CA3062194A1 - Method of treating or ameliorating metabolic disorders using binding proteins for gastric inhibitory peptide receptor (gipr) in combination with glp-1 agonists - Google Patents

Abstract

Methods of treating metabolic diseases and disorders using an antigen binding protein specific for the GIPR polypeptide are provided. In various embodiments the metabolic disease or disorder is type 2 diabetes, obesity, dyslipidemia, elevated glucose levels, elevated insulin levels and diabetic nephropathy. In certain embodiments the antigen binding protein is administered in combination with a GLP-1 receptor agonist.

Description

DEMANDE OU BREVET VOLUMINEUX
LA PRESENTE PARTIE DE CETTE DEMANDE OU CE BREVET COMPREND
PLUS D'UN TOME.

NOTE : Pour les tomes additionels, veuillez contacter le Bureau canadien des brevets JUMBO APPLICATIONS/PATENTS
THIS SECTION OF THE APPLICATION/PATENT CONTAINS MORE THAN ONE
VOLUME

NOTE: For additional volumes, please contact the Canadian Patent Office NOM DU FICHIER / FILE NAME:
NOTE POUR LE TOME / VOLUME NOTE:

METHOD OF TREATING OR AMELIORATING METABOLIC DISORDERS USING
BINDING PROTEINS FOR GASTRIC INHIBITORY PEPTIDE RECEPTOR (GIPR) FIELD OF THE INVENTION
[0001] The present disclosure relates to the treatment or amelioration of a metabolic disorder, such as type 2 diabetes, elevated glucose levels, elevated insulin levels, obesity, non-alcoholic fatty liver disease, or cardiovascular diseases, using an antigen binding protein specific for the gastric inhibitory peptide receptor (GIPR).
BACKGROUND OF THE INVENTION

[0002] Glucose-dependent insulinotropic polypeptide (GIP) is a single 42-amino acid peptide secreted from K-cells in the small intestine (duodenum and jejunum). Human GIP
is derived from the processing of proGIP, a 153-amino acid precursor that is encoded by a gene localized to chromosome 17q (Inagaki et al., Mol Endocrinol 1989; 3:1014-1021;
Fehmann et al. Endocr Rev. 1995; 16:390-410). GIP was formerly called gastric inhibitory polypeptide.

[0003] GIP secretion is induced by food ingestion. GIP has a number of physiological effects in tissues, including promotion of fat storage in adipocytes and promotion of pancreatic islet 13-cell function and glucose-dependent insulin secretion. GIP and glucagon like polypeptide-1 (GLP-1) are known insulinotropic factors ("incretins"). Intact GIP is rapidly degraded by DPPIV to an inactive form. The insulinotropic effect of GIP is lost in type 2 diabetic patients while GLP-1's incretin effect remains intact (Nauck et al. J. Clinc. Invest.
1993; 91:301-307).

[0004] The GIP receptor (GIPR) is a member of the secretin-glucagon family of G-protein coupled receptors (GPCRs) having an extracellular N-terminus, seven transmembrane domains and an intracellular C-terminus. The N-terminal extracellular domains of this family of receptors are usually glycosylated and form the recognition and binding domain of the receptor. GIPR is highly expressed in a number of tissues, including the pancreas, gut, adipose tissue, heart, pituitary, adrenal cortex, and brain (Usdin et al., Endocrinology. 1993, 133:2861-2870). Human GIPR comprises 466 amino acids and is encoded by a gene located on chromosome 19q13.3 (Gremlich et al., Diabetes. 1995; 44:1202-8; Volz et al., FEBS Lett.
1995, 373:23-29). Studies have suggested that alternative mRNA splicing results in the production of GIP receptor variants of differing lengths in human, rat and mouse.

[0005] GIPR knockout mice (Gipr 4-) are resistant to high fat diet-induced weight gain and have improved insulin sfensitivity and lipid profiles. (Yamada et al., Diabetes. 2006, 55:S86;
Miyawaki et al. Nature Med. 2002, 8:738-742). In addition, a novel small molecule GIPR
antagonist SKL-14959 prevents obesity and insulin resistance. (Diabetologia 2008, 51:S373, 44th EASD Annual meeting poster).

[0006] Glucagon-like peptide-1 ("GLP-1") is a 31-amino acid peptide derived from the proglucagon gene. It is secreted by intestinal L-cells and released in response to food ingestion to induce insulin secretion from pancreatic f3 - cells (Diabetes 2004, 53:S3, 205-214). In addition to the incretin effects, GLP-1 also decreases glucagon secretion, delays gastric emptying and reduces caloric intake (Diabetes Care, 2003, 26(10): 2929-2940). GLP-1 exerts its effects by activation of the GLP-1 receptor, which belongs to a class B G-protein-coupled receptor (Endocrinology. 1993, 133(4):1907-10). The function of GLP-1 is limited by rapid degradation by the DPP-IV enzyme, resulting in a half-life of approximately 2 minutes. Recently, long-lasting GLP-1 receptor agonists such as exenatide, liraglutide, dulaglutide have been developed and are now being used clinically to improve glycemic control in patients with type 2 diabetes. Furthermore, GLP-1 receptor agonists also promote body weight reduction as well as reduction in blood pressure and plasma cholesterol levels in patients (Bioorg. Med. Chem.Lett 2013, 23:4011-4018).

[0007] Collectively, these links to obesity and insulin resistance imply GIPR
inhibition is a useful approach for therapeutic intervention, both as a monotherapy and in combination with GLP-1.
SUMMARY OF THE INVENTION

[0008] In one aspect, the present disclosure provides a method of treating a subject with a metabolic disorder, the method comprising administering to the subject a therapeutically effective amount of an antigen binding protein that specifically binds to a protein having an amino acid sequence having at least 90% amino acid sequence identity to an amino acid sequence of a GIPR. In one aspect the present invention is directed to a method of treating a subject with a metabolic disorder, the method comprising administering to the subject a therapeutically effective amount of a GLP-1 receptor agonist and a therapeutically effective amount of a GIPR antagonist that specifically binds to a protein having an amino acid sequence having at least 90% amino acid sequence identity to an amino acid sequence of a GIPR. In one embodiment, the metabolic disorder is a disorder of glucose metabolism. In another embodiment, the glucose metabolism disorder comprises hyperglycemia and administering the antigen binding protein reduces plasma glucose. In another embodiment, the glucose metabolism disorder comprises hyperinsulinemia and administering the antigen binding protein reduces plasma insulin. In another embodiment, the glucose metabolism disorder comprises glucose intolerance and administering the antigen binding protein reduces increases glucose tolerance. In another embodiment, the glucose metabolism disorder comprises insulin resistance and administering the antigen binding protein reduces insulin resistance. In another embodiment, the glucose metabolism disorder comprises diabetes mellitus. In another embodiment, the subject is obese. In another embodiment, administering the antigen binding protein reduces body weight in an obese subject. In another embodiment, administering the antigen binding protein reduces body weight gain in an obese subject. In another embodiment, administering the antigen binding protein reduces fat mass in an obese subject. In another embodiment, the glucose metabolism disorder comprises insulin resistance and administering the antigen binding protein reduces insulin resistance in an obese subject.
In another embodiment, administering the antigen binding protein reduces liver steatosis in an obese subject having increased liver steatosis. In another embodiment, administering the antigen binding protein reduces liver fat content in an obese subject having increased liver fat content.

[0009] In one aspect the present invention is directed to a method of treatment comprising administering to a subject a therapeutically effective amount of at least one GLP-1 receptor agonist in combination with administration of at least one GIPR antagonist which upon administration to a subject with symptoms of a metabolic disorder provides sustained beneficial effects.

[0010] In one embodiment, administration of at least one GLP-1 receptor agonist in combination with administration of at least one GIPR antagonist provides sustained beneficial effects of at least one symptom of a metabolic disorder.

[0011] In one embodiment, the therapeutically effective amounts of the GLP-1 receptor agonist and the GIPR antagonist are combined prior to administration to the subject.

[0012] In one embodiment, the therapeutically effective amounts of the GLP-1 receptor agonist and the GIPR antagonist are administered to the subject sequentially.

[0013] In one embodiment, the therapeutically effective amounts of a GLP-1 receptor agonist and a GIPR antagonist are synergistically effective amounts.

[0014] In one embodiment, the molar ratio of a GLP-1 receptor agonist to a GIPR antagonist is from about 1:1 to 1:110, 1:1 to 1:100, 1:1 to 1:75, 1:1 to 1:50, 1:1 to 1:25, 1:1 to 1:10, 1:1 to 1:5, and 1:1. In one embodiment, the molar ratio of a GIPR antagonist to a GLP-1 receptor agonist is from about 1:1 to 1:110, 1:1 to 1:100, 1:1 to 1:75, 1:1 to 1:50, 1:1 to 1:25, 1:1 to 1:10, and 1:1 to 1:5.

[0015] In one embodiment, the GLP-1 receptor agonist is used in combination with the GIPR
antagonist at therapeutically effective molar ratios of between about 1:1.5 to 1:150, preferably 1:2 to 1:50.

[0016] In one embodiment, the GLP-1 receptor agonist and the GIPR antagonist are present in doses that are at least about 1.1 to 1.4, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, or 10 fold lower than the doses of each compound alone required to treat a condition and/or disease.

[0017] In one embodiment, the GLP-1 receptor agonist is GLP-1(7-37) or a GLP-1(7-37) analog.

[0018] In one embodiment, the GLP-1 receptor agonist is selected from the group consisting of exenatide, liraglutide, lixisenatide, albiglutide, dulaglutide, semaglutide, and taspoglutide.

[0019] In one embodiment, the GLP-1 receptor agonist is selected from the group consisting of GLP-1(7-37) (SEQ ID NO: 1244); GLP-1(7-36)-N}2 (SEQ ID NO: 1245);
iiraglutide;
albiglutide; taspoglutid.e; dulaglutide, semaglutide, LY2428757; desamino-His7,.. 2Arg 6,Lys34(Ne_7,, Glu(N-a-hexadecanoyI)))-GLP-1(7-37) (core peptide disclosed as SEQ ID NO: 1282); desamino-Illis7,Arg26,Lys34(Nc-octanoy1)-GLP-1(7-37) (SEQ ID
NO:
1283); Arg26,34,Lys38(M-(a)-carboxypentadecan.oy1))-GLP-1(7-38) (SEQ ID NO:
1284);
Arg26,34,Lys36(Ne./y_ Giu(N-a-hexadecanoy1)))-GLP-1(7-36) (core peptide disclosed as SEQ
ID NO: 1285); Aib8,35,Arg26,34,Phe31-GLP-1(7-36)) (SEQ ID NO: 1246);
FIXaa8EGTFTSDV5SYLEXaa22Xaa23AAKEFIXaa3oWLXaa33Xaa34G Xaa36Xaa37; wherein Xaa3 is A, V, or Gr; Xaa.22 is G, K, or E; Xaa.23 is Q or K; Xaa:30 is A or E;
Xaa33 is V or K;
Xaa34 is K, N, or R; Xaa36 is R or G; and Xaa37 is G. H, P, or absent (SEQ ID
NO: 1247);
Arg34-GLP-I(7.37) (SEQ ID NO: 1248); G1u30-GLP-1(7-37) (SEQ ID NO: 1249);
Lys22-GLP-1(7-37) (SEQ ID NO: 1250); Gly8.36,G1u22-GLP-1(7-37) (SEQ ID NO: 1.251);
u22, y GLP-1(7-37) (SEQ ID NO: 1252); Gly8s36,G1u22,Lys33,.Asn34-GLP-1(7-37) (SEQ ID NO: 1253); Va18,G1u22,Lys33,Asn34,G1y36-GLP-1(7-37) (SEQ ID NO: 1254);

Gly8,36,G1u22,Pro37-GLP-1(7-37) (SEQ ID NO: 1255); 'Va18,G1u22,G1y36Pro37-GLP-1(7-37) (SEQ ID NO: 1256); Gly8,36,G1u22,Lys33, Asn34,Pro37-GLP-I(7-37) (SEQ ID NO:
1257);
va18,Giu22,Lys33,Asn34,Gly36,Pro37-GLP-1(7-37) (SEQ ID NO: 1258); Gly 8,36, Giu22_GLp_1(7_ 36) (SEQ ID NO: 1259); Va18,Glu22,G1y36-GILP-1(7-36) (SEQ ID NO: 1260);
Va18,G1u22,.Asn34,Gly36-GLP-1(7-36) (SEQ ID NO: 1261); and Gly8,36,G1u22,Asn34-GLP-1(7-36) (SEQ ID NO: 1262).

[0020] In another embodiment, the subject is a mammal. In another embodiment, the subject is human. In another embodiment, the GIPR is human GIPR. In another embodiment, the administering is by parenteral injection. In another embodiment, the administering is by subcutaneous injection.

[0021] In another aspect the present disclosure provides an antigen binding protein that specifically binds to a human GIPR polypeptide and inhibits activation of GIPR
by GIP
ligand. In one embodiment, the antigen binding protein inhibits GIP ligand binding to GIPR.
In another embodiment, the antigen binding protein is a human antigen binding protein. In another embodiment, the antigen binding protein is a human antibody. In another embodiment, the antigen binding protein is a monoclonal antibody.

[0022] In another aspect, the present disclosure provides a pharmaceutical composition comprising at least one antigen binding protein according to any one of the foregoing embodiments.

[0023] In another aspect, the present disclosure provides a nucleic acid molecule encoding an antigen binding protein according to any one of the foregoing embodiments.

[0024] In another aspect, the present disclosure provides a vector comprising a nucleic acid molecule encoding an antigen binding protein according to any one of the foregoing embodiments.

[0025] In another aspect, the present disclosure provides a host cell comprising a nucleic acid molecule encoding an antigen binding protein according to any one of the foregoing embodiments or a vector comprising a nucleic acid molecule encoding an antigen binding protein according to any one of the foregoing embodiments. In another aspect the present disclosure provides an antigen binding protein that specifically binds to a human GIPR
polypeptide expressed by the vector.

[0026] In another aspect, the present disclosure provides a method of making an antigen binding protein according to any one of the foregoing embodiments, the method comprising expressing the antigen binding protein in a host cell that secretes the antigen binding protein, and then purifying the antigen binding protein from the cell culture media. In another aspect the present disclosure provides an antigen binding protein that specifically binds to a human GIPR polypeptide purified from the host cell.

[0027] In another aspect, the present disclosure provides an antigen binding protein of any one of the foregoing embodiments or a pharmaceutical composition of any one of the foregoing embodiments for use in therapy.

DETAILED DESCRIPTION OF THE INVENTION

[0028] The present disclosure provides a method of treating a metabolic disorder, such as a disorder of glucose metabolism (e.g. Type 2 diabetes, elevated glucose levels, elevated insulin levels, dyslipidemia, metabolic syndrome (Syndrome X or insulin resistance syndrome), glucosuria, metabolic acidosis, Type 1 diabetes, obesity and conditions exacerbated by obesity) by blocking or interfering with the biological activity of GIP. In one embodiment, a therapeutically effective amount of an isolated human GIPR
binding protein is administered to a subject in need thereof Methods of administration and delivery are also provided.

[0029] Recombinant polypeptide and nucleic acid methods used herein, including in the Examples, are generally those set forth in Sambrook et al., Molecular Cloning:
A Laboratory Manual (Cold Spring Harbor Laboratory Press, 1989) or Current Protocols in Molecular Biology (Ausubel et al., eds., Green Publishers Inc. and Wiley and Sons 1994), both of which are incorporated herein by reference for any purpose.

[0030] The section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described.

[0031] Unless otherwise defined herein, scientific and technical terms used in connection with the present application shall have the meanings that are commonly understood by those of ordinary skill in the art. Further, unless otherwise required by context, singular terms shall include pluralities and plural terms shall include the singular.

[0032] Generally, nomenclatures used in connection with, and techniques of, cell and tissue culture, molecular biology, immunology, microbiology, genetics and protein and nucleic acid chemistry and hybridization described herein are those well-known and commonly used in the art. The methods and techniques of the present application are generally performed according to conventional methods well known in the art and as described in various general and more specific references that are cited and discussed throughout the present specification unless otherwise indicated. See, e.g., Sambrook et al., Molecular Cloning: A
Laboratory Manual, 3rd ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.
(2001), Ausubel et al., Current Protocols in Molecular Biology, Greene Publishing Associates (1992), and Harlow and Lane Antibodies: A Laboratory Manual Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. (1990), which are incorporated herein by reference.
Enzymatic reactions and purification techniques are performed according to manufacturer's specifications, as commonly accomplished in the art or as described herein.
The terminology used in connection with, and the laboratory procedures and techniques of, analytical chemistry, synthetic organic chemistry, and medicinal and pharmaceutical chemistry described herein are those well-known and commonly used in the art. Standard techniques can be used for chemical syntheses, chemical analyses, pharmaceutical preparation, formulation, and delivery, and treatment of patients.

[0033] It should be understood that this invention is not limited to the particular methodology, protocols, and reagents, etc., described herein and as such may vary. The terminology used herein is for the purpose of describing particular embodiments only, and is not intended to limit the scope of the disclosed, which is defined solely by the claims.

[0034] Other than in the operating examples, or where otherwise indicated, all numbers expressing quantities of ingredients or reaction conditions used herein should be understood as modified in all instances by the term "about." The term "about" when used in connection with percentages may mean 1%.

[0035] Following convention, as used herein "a" and "an" mean "one or more"
unless specifically indicated otherwise.

[0036] As used herein, the terms "amino acid" and "residue" are interchangeable and, when used in the context of a peptide or polypeptide, refer to both naturally occurring and synthetic amino acids, as well as amino acid analogs, amino acid mimetics and non-naturally occurring amino acids that are chemically similar to the naturally occurring amino acids.

[0037] A "naturally occurring amino acid" is an amino acid that is encoded by the genetic code, as well as those amino acids that are encoded by the genetic code that are modified after synthesis, e.g., hydroxyproline, y-carboxyglutamate, and 0-phosphoserine. An amino acid analog is a compound that has the same basic chemical structure as a naturally occurring amino acid, i.e., an a carbon that is bound to a hydrogen, a carboxyl group, an amino group, and an R group, e.g., homoserine, norleucine, methionine sulfoxide, methionine methyl sulfonium. Such analogs can have modified R groups (e.g., norleucine) or modified peptide backbones, but will retain the same basic chemical structure as a naturally occurring amino acid.

[0038] An "amino acid mimetic" is a chemical compound that has a structure that is different from the general chemical structure of an amino acid, but that functions in a manner similar to a naturally occurring amino acid. Examples include a methacryloyl or acryloyl derivative of an amide, (3-, y-, 6-amino acids (such as piperidine-4-carboxylic acid) and the like.

[0039] A "non-naturally occurring amino acid" is a compound that has the same basic chemical structure as a naturally occurring amino acid, but is not incorporated into a growing polypeptide chain by the translation complex. "Non-naturally occurring amino acid" also includes, but is not limited to, amino acids that occur by modification (e.g., posttranslational modifications) of a naturally encoded amino acid (including but not limited to, the 20 common amino acids) but are not themselves naturally incorporated into a growing polypeptide chain by the translation complex. A non-limiting lists of examples of non-naturally occurring amino acids that can be inserted into a polypeptide sequence or substituted for a wild-type residue in polypeptide sequence include 13-amino acids, homoamino acids, cyclic amino acids and amino acids with derivatized side chains. Examples include (in the L-form or D-form; abbreviated as in parentheses): citrulline (Cit), homocitrulline (hCit), Na-methylcitrulline (NMeCit), Na-methylhomocitrulline (Na-MeHoCit), ornithine (Orn), Na-Methylornithine (Na-MeOrn or NMeOrn), sarcosine (Sar), homolysine (hLys or hK), homoarginine (hArg or hR), homoglutamine (hQ), Na-methylarginine (NMeR), Na-methylleucine (Na-MeL or NMeL), N-methylhomolysine (NMeHoK), Na-methylglutamine (NMeQ), norleucine (Nle), norvaline (Nva), 1,2,3,4-tetrahydroisoquinoline (Tic), Octahydroindole-2-carboxylic acid (Oic), 3-(1-naphthyDalanine (1-Nal), 3-(2-naphthyDalanine (2-Nal), 1,2,3,4-tetrahydroisoquinoline (Tic), 2-indanylglycine (IgI), para-iodophenylalanine (pI-Phe), para-aminophenylalanine (4AmP or 4-Amino-Phe), 4-guanidino phenylalanine (Guf), glycyllysine (abbreviated "K(NE-glycyl)" or "K(glycyl)" or "K(gly)"), nitrophenylalanine (nitrophe), aminophenylalanine (aminophe or Amino-Phe), benzylphenylalanine (benzylphe), y-carboxyglutamic acid (y-carboxyglu), hydroxyproline (hydroxypro), p-carboxyl-phenylalanine (Cpa), a-aminoadipic acid (Aad), Na-methyl valine (NMeVal), N-a-methyl leucine (NMeLeu), Na-methylnorleucine (NMeNle), cyclopentylglycine (Cpg), cyclohexylglycine (Chg), acetylarginine (acetylarg), a, 13-diaminopropionoic acid (Dpr), a, y-diaminobutyric acid (Dab), diaminopropionic acid (Dap), cyclohexylalanine (Cha), 4-methyl-phenylalanine (MePhe), 13, 13-diphenyl-alanine (BiPhA), aminobutyric acid (Abu), 4-phenyl-phenylalanine (or biphenylalanine; 4Bip), a-amino-isobutyric acid (Aib), beta-alanine, beta-aminopropionic acid, piperidinic acid, aminocaprioic acid, aminoheptanoic acid, aminopimelic acid, desmosine, diaminopimelic acid, N-ethylglycine, N-ethylaspargine, hydroxylysine, allo-hydroxylysine, isodesmosine, allo-isoleucine, N-methylglycine, N-methylisoleucine, N-methylvaline, 4-hydroxyproline (Hyp), y-carboxyglutamate, e-N,N,N-trimethyllysine, e-N-acetyllysine, 0-phosphoserine, N-acetylserine, N-formylmethionine, 3-methylhistidine, 5-hydroxylysine, w-methylarginine, 4-Amino-O-Phthalic Acid (4APA), and other similar amino acids, and derivatized forms of any of those specifically listed.

[0040] The term "isolated nucleic acid molecule" refers to a single or double-stranded polymer of deoxyribonucleotide or ribonucleotide bases read from the 5' to the 3' end (e.g., a GIPR nucleic acid sequence provided herein), or an analog thereof, that has been separated from at least about 50 percent of polypeptides, peptides, lipids, carbohydrates, polynucleotides or other materials with which the nucleic acid is naturally found when total nucleic acid is isolated from the source cells. Preferably, an isolated nucleic acid molecule is substantially free from any other contaminating nucleic acid molecules or other molecules that are found in the natural environment of the nucleic acid that would interfere with its use in polypeptide production or its therapeutic, diagnostic, prophylactic or research use.

[0041] The term "isolated polypeptide" refers to a polypeptide (e.g., a GIPR
polypeptide sequence provided herein or an antigen binding protein of the present invention) that has been separated from at least about 50 percent of polypeptides, peptides, lipids, carbohydrates, polynucleotides, or other materials with which the polypeptide is naturally found when isolated from a source cell. Preferably, the isolated polypeptide is substantially free from any other contaminating polypeptides or other contaminants that are found in its natural environment that would interfere with its therapeutic, diagnostic, prophylactic or research use.

[0042] The term "encoding" refers to a polynucleotide sequence encoding one or more amino acids. The term does not require a start or stop codon.

[0043] The terms "identical" and percent "identity," in the context of two or more nucleic acids or polypeptide sequences, refer to two or more sequences or subsequences that are the same. "Percent identity" means the percent of identical residues between the amino acids or nucleotides in the compared molecules and is calculated based on the size of the smallest of the molecules being compared. For these calculations, gaps in alignments (if any) can be addressed by a particular mathematical model or computer program (i.e., an "algorithm").
Methods that can be used to calculate the identity of the aligned nucleic acids or polypeptides include those described in Computational Molecular Biology, (Lesk, A. M., ed.), (1988) New York: Oxford University Press; Biocomputing Informatics and Genome Projects, (Smith, D.
W., ed.), 1993, New York: Academic Press; Computer Analysis of Sequence Data, Part I, (Griffin, A. M., and Griffin, H. G., eds.), 1994, New Jersey: Humana Press;
von Heinje, G., (1987) Sequence Analysis in Molecular Biology, New York: Academic Press;
Sequence Analysis Primer, (Gribskov, M. and Devereux, J., eds.), 1991, New York: M.
Stockton Press;
and Carillo etal., (1988) SIAM J. Applied Math. 48:1073.

[0044] In calculating percent identity, the sequences being compared are aligned in a way that gives the largest match between the sequences. The computer program used to determine percent identity is the GCG program package, which includes GAP (Devereux et al., (1984) Nucl. Acid Res. 12:387; Genetics Computer Group, University of Wisconsin, Madison, WI).
The computer algorithm GAP is used to align the two polypeptides or polynucleotides for which the percent sequence identity is to be determined. The sequences are aligned for optimal matching of their respective amino acid or nucleotide (the "matched span", as determined by the algorithm). A gap opening penalty (which is calculated as 3x the average diagonal, wherein the "average diagonal" is the average of the diagonal of the comparison matrix being used; the "diagonal" is the score or number assigned to each perfect amino acid match by the particular comparison matrix) and a gap extension penalty (which is usually 1/10 times the gap opening penalty), as well as a comparison matrix such as PAM 250 or BLOSUM 62 are used in conjunction with the algorithm. In certain embodiments, a standard comparison matrix (see, Dayhoff et al., (1978) Atlas of Protein Sequence and Structure 5:345-352 for the PAM 250 comparison matrix; Henikoff et al., (1992) Proc.
Natl. Acad. Sci.
U.S.A. 89:10915-10919 for the BLOSUM 62 comparison matrix) is also used by the algorithm.

[0045] Recommended parameters for determining percent identity for polypeptides or nucleotide sequences using the GAP program are the following:

[0046] Algorithm: Needleman et al., 1970, J. Mol. Biol. 48:443-453;

[0047] Comparison matrix: BLOSUM 62 from Henikoff et al., 1992, supra;

[0048] Gap Penalty: 12 (but with no penalty for end gaps)

[0049] Gap Length Penalty: 4

[0050] Threshold of Similarity: 0

[0051] Certain alignment schemes for aligning two amino acid sequences can result in matching of only a short region of the two sequences, and this small aligned region can have very high sequence identity even though there is no significant relationship between the two full-length sequences. Accordingly, the selected alignment method (e.g., the GAP program) can be adjusted if so desired to result in an alignment that spans at least 50 contiguous amino acids of the target polypeptide.

[0052] The terms "GIPR polypeptide" and "GIPR protein" are used interchangeably and mean a naturally-occurring wild-type polypeptide expressed in a mammal, such as a human or a mouse, and includes naturally occurring alleles (e.g., naturally occurring allelic forms of human GIPR protein). For purposes of this disclosure, the term "GIPR
polypeptide" can be used interchangeably to refer to any full-length GIPR polypeptide, e.g., SEQ
ID NO: 1201, which consists of 466 amino acid residues and which is encoded by the nucleotide sequence SEQ ID NO: 1202, or SEQ ID NO: 1203, which consists of 430 amino acid residues and which is encoded by the nucleic acid sequence SEQ ID NO: 1204, or SEQ ID NO:
1205, which consists of 493 amino acid resides and which is encoded by the nucleic acid sequence of SEQ ID NO: 1206, or SEQ ID NO: 1207, which consists of 460 amino acids residues and which is encoded by the nucleic acid sequence of SEQ ID NO: 1208, or SEQ ID
NO: 1209, which consists of 230 amino acids residues and which is encoded by the nucleic acid sequence of SEQ ID NO: 1210.

[0053] The term "GIPR polypeptide" also encompasses a GIPR polypeptide in which a naturally occurring GIPR polypeptide sequence (e.g., SEQ ID NOs: 1201, 1203 or 1205) has been modified. Such modifications include, but are not limited to, one or more amino acid substitutions, including substitutions with non-naturally occurring amino acids non-naturally-occurring amino acid analogs and amino acid mimetics.

[0054] In various embodiments, a GIPR polypeptide comprises an amino acid sequence that is at least about 85 percent identical to a naturally-occurring GIPR
polypeptide (e.g., SEQ ID
NOs: 1201, 1203 or 1205). In other embodiments, a GIPR polypeptide comprises an amino acid sequence that is at least about 90 percent, or about 95, 96, 97, 98, or 99 percent identical to a naturally-occurring GIPR polypeptide amino acid sequence (e.g., SEQ ID
NOs: 1201, 1203 or 1205). Such GIPR polypeptides preferably, but need not, possess at least one activity of a wild-type GIPR polypeptide, such as the ability to bind GIP. The present invention also encompasses nucleic acid molecules encoding such GIPR polypeptide sequences.

[0055] The terms "GIPR activity assay" (also referred to as a "GIPR functional assay") means an assay that can be used to measure GIP or a GIP binding protein activity in a cellular setting. In one embodiment, the "activity" (or "functional") assay" can be a cAMP assay in GIPR expressing cells, in which GIP can induce cAMP signal, and the activity of a GIP/GIPR binding protein could be measured in the presence/absence of GIP
ligand, in which IC50/EC50 and degree of inhibition/activation can be obtained (Biochemical and Biophysical Research Communications (2002) 290:1420-1426). In another embodiment, the "activity" (or "functional") assay can be an insulin secretion assay in pancreatic beta cells, in which GIP can induce glucose-dependent insulin secretion, and the activity of a GIP/GIPR
binding protein could be measured in the presence/absence of GIP ligand, in which IC50/EC50 and degree of inhibition/activation can be obtained (Biochemical and Biophysical Research Communications (2002) 290:1420-1426).

[0056] The term "GIPR binding assay" means an assay that can be used to measure binding of GIP to GIPR. In one embodiment, "GIPR binding assay" can be an assay using FMAT or FACS that measures fluorescence-labeled GIP binding to GIPR expression cells, and GIP/GIPR binding protein's activity can be measured for displacing fluorescence-labeled GIP
binding to GIPR expression cells. In another embodiment, "GIPR binding assay"
can be an assay that measures radioactive-labeled GIP binding to GIPR expression cells, and GIP/GIPR
binding protein's activity can be measured for displacing radioactive labeled GIP binding to GIPR expression cells (Biochimica et Biophysica Acta (2001) 1547:143-155).

[0057] The terms "GIP", "Gastric inhibitory polypeptide", "glucose-dependent insulinotropic peptide" and "GIP ligand" are used interchangeably and mean a naturally-occurring wild-type polypeptide expressed in a mammal, such as a human or a mouse, and includes naturally occurring alleles (e.g., naturally occurring allelic forms of human GIP
protein). For purposes of this disclosure, the term "GIP" can be used interchangeably to refer to any mature GIP
polypeptide.

[0058] The 42 amino acid sequence of mature human GIP is:

[0059] YAEGTFISDY SIAMDKIHQQ DFVNWLLAQK GKKNDWKHNI TQ (M)1131\14a 1211)

[0060] and is encoded by the DNA sequence:

[0061] tatgcggaag gcacctttat tagcgattat agcattgcga tggataaaat tcatcagcag gattttgtga actggctgct ggcgcagaaa ggcaaaaaaa acgattggaa acataacatt acccag (SEQ ID NO: 1212).

[0062] The 42 amino acid sequence of mature murine GIP is:

[0063] YAEGTFISDY SIAMDKIRQQ DFVNWLLAQR GKKSDWKHNI TQ (SEQ ID NO:
1213)

[0064] and is encoded by the DNA sequence:

[0065] tatgcggaag gcacctttat tagcgattat agcattgcga tggataaaat tcgccagcag gattttgtga actggctgct ggcgcagcgc ggcaaaaaaa gcgattggaa acataacatt acccag (SEQ ID NO: 1214).

[0066] The 42 amino acid sequence of mature rat GIP is:
100671 YAEGTFISDY SIAMDKIRQQ DFVNWLLAQK GKKNDWKHNL TQ(SWIDMI
1215) [0068] and is encoded by the DNA sequence:
[0069] tatgcggaag gcacctttat tagcgattat agcattgcga tggataaaat tcgccagcag gattttgtga actggctgctg gcgcagaaag gcaaaaaaaa cgattggaaa cataacctga cccag (SEQ IDNO: 1216).
[0070] An "antigen binding protein" as used herein means any protein that specifically binds a specified target antigen, such as a GIPR polypeptide (e.g., a human GIPR
polypeptide such as provided in SEQ ID NOs: 1201, 1203 or 1205). The term encompasses intact antibodies that comprise at least two full-length heavy chains and two full-length light chains, as well as derivatives, variants, fragments, and mutations thereof Examples of antibody fragments include Fab, Fab', F(ab1)2, and Fv fragments. An antigen binding protein also includes domain antibodies such as nanobodies and scFvs as described further below.
[0071] In general, a GIPR antigen binding protein is said to "specifically bind" its target antigen GIPR when the antigen binding protein exhibits essentially background binding to non-GIPR molecules. An antigen binding protein that specifically binds GIPR
may, however, cross-react with GIPR polypeptides from different species. Typically, a GIPR
antigen binding protein specifically binds human GIPR when the dissociation constant (KD) is <10-7M as measured via a surface plasma resonance technique (e.g., BIACore, GE-Healthcare Uppsala, Sweden) or Kinetic Exclusion Assay (KinExA, Sapidyne, Boise, Idaho). A GIPR
antigen binding protein specifically binds human GIPR with "high affinity" when the KD
is <5x 10-9 M, and with "very high affinity" when the KD is <5x 10-19 M, as measured using methods described.
[0072] "Antigen binding region" means a protein, or a portion of a protein, that specifically binds a specified antigen. For example, that portion of an antigen binding protein that contains the amino acid residues that interact with an antigen and confer on the antigen binding protein its specificity and affinity for the antigen is referred to as "antigen binding region." An antigen binding region typically includes one or more "complementary binding regions" ("CDRs") of an immunoglobulin, single-chain immunoglobulin, or camelid antibody. Certain antigen binding regions also include one or more "framework"
regions. A
"CDR" is an amino acid sequence that contributes to antigen binding specificity and affinity.
"Framework" regions can aid in maintaining the proper conformation of the CDRs to promote binding between the antigen binding region and an antigen.
[0073] A "recombinant protein", including a recombinant GIPR antigen binding protein, is a protein made using recombinant techniques, i.e., through the expression of a recombinant nucleic acid as described herein. Methods and techniques for the production of recombinant proteins are well known in the art.
[0074] The term "antibody" refers to an intact immunoglobulin of any isotype, or a fragment thereof that can compete with the intact antibody for specific binding to the target antigen, and includes, for instance, chimeric, humanized, fully human, and bispecific antibodies. An "antibody" as such is a species of an antigen binding protein. An intact antibody generally will comprise at least two full-length heavy chains and two full-length light chains.
Antibodies may be derived solely from a single source, or may be "chimeric,"
that is, different portions of the antibody may be derived from two different antibodies as described further below. The antigen binding proteins, antibodies, or binding fragments may be produced in hybridomas, by recombinant DNA techniques, or by enzymatic or chemical cleavage of intact antibodies.
[0075] The term "light chain" as used with respect to an antibody or fragments thereof includes a full-length light chain and fragments thereof having sufficient variable region sequence to confer binding specificity. A full-length light chain includes a variable region domain, VL, and a constant region domain, CL. The variable region domain of the light chain is at the amino-terminus of the polypeptide. Light chains include kappa chains and lambda chains.
[0076] The term "heavy chain" as used with respect to an antibody or fragment thereof includes a full-length heavy chain and fragments thereof having sufficient variable region sequence to confer binding specificity. A full-length heavy chain includes a variable region domain, VH, and three constant region domains, CH1, CH2, and CH3. The VH
domain is at the amino-terminus of the polypeptide, and the CH domains are at the carboxyl-terminus, with the CH3 being closest to the carboxy-terminus of the polypeptide. Heavy chains may be of any isotype, including IgG (including IgGl, IgG2, IgG3 and IgG4 subtypes), IgA
(including IgAl and IgA2 subtypes), IgM and IgE.
[0077] The term "immunologically functional fragment" (or simply "fragment") of an antibody or immunoglobulin chain (heavy or light chain), as used herein, is an antigen binding protein comprising a portion (regardless of how that portion is obtained or synthesized) of an antibody that lacks at least some of the amino acids present in a full-length chain but which is capable of specifically binding to an antigen. Such fragments are biologically active in that they bind specifically to the target antigen and can compete with other antigen binding proteins, including intact antibodies, for specific binding to a given epitope.

[0078] These biologically active fragments may be produced by recombinant DNA
techniques, or may be produced by enzymatic or chemical cleavage of antigen binding proteins, including intact antibodies. Immunologically functional immunoglobulin fragments include, but are not limited to, Fab, Fab', and F(ab1)2 fragments.
[0079] In another embodiment, Fvs, domain antibodies and seFvs, and may be derived from an antibody of the present invention.
[0080] It is contemplated further that a functional portion of the antigen binding proteins disclosed herein, for example, one or more CDRs, could be covalently bound to a second protein or to a small molecule to create a therapeutic agent directed to a particular target in the body, possessing bifunctional therapeutic properties, or having a prolonged serum half-life.
[0081] A "Fab fragment" is comprised of one light chain and the CH1 and variable regions of one heavy chain. The heavy chain of a Fab molecule cannot form a disulfide bond with another heavy chain molecule.
[0082] An "Fe" region contains two heavy chain fragments comprising the CH2 and CH3 domains of an antibody. The two heavy chain fragments are held together by two or more disulfide bonds and by hydrophobic interactions of the CH3 domains.
[0083] In certain embodiments, one or more amino acid modifications may be introduced into the Fc region of an antibody provided herein, thereby generating an Fc region variant.
The Fc region variant may comprise a human Fc region sequence (e.g., a human IgGl, IgG2, IgG3 or IgG4 Fc region) comprising an amino acid modification (e.g. a substitution) at one or more amino acid positions.
[0084] In certain embodiments, the invention contemplates an antibody variant that possesses some but not all effector functions, which make it a desirable candidate for applications in which the half life of the antibody in vivo is important yet certain effector functions (such as complement and ADCC) are unnecessary or deleterious. In vitro and/or in vivo cytotoxicity assays can be conducted to confirm the reduction/depletion of CDC and/or ADCC
activities.
For example, Fc receptor (FcR) binding assays can be conducted to ensure that the antibody lacks Fc.gamma.R binding (hence likely lacking ADCC activity), but retains FcRn binding ability. The primary cells for mediating ADCC, NK cells, express Fe(RIII only, whereas monocytes express Fe(RI, Fe(RII and Fe(RIII. FcR expression on hematopoietic cells is summarized in Table 3 on page 464 of Ravetch and Kinet, Annu. Rev. Immunol.
9:457-492 (1991). Non-limiting examples of in vitro assays to assess ADCC activity of a molecule of interest is described in U.S. Pat. No. 5,500,362 (see, e.g. Hellstrom, I. et al. Proc. Nat'l Acad.

Sci. USA 83:7059-7063 (1986)) and Hellstrom, I et al., Proc. Nat'l Acad. Sci.
USA 82:1499-1502 (1985); 5,821,337 (see Bruggemann, M. etal., J. Exp. Med. 166:1351-1361 (1987)).
Alternatively, non-radioactive assays methods may be employed (see, for example, ACTI.TM. non-radioactive cytotoxicity assay for flow cytometry (CellTechnology, Inc.
Mountain View, Calif.; and CytoTox 96® non-radioactive cytotoxicity assay (Promega, Madison, Wis.). Useful effector cells for such assays include peripheral blood mononuclear cells (PBMC) and Natural Killer (NK) cells. Alternatively, or additionally, ADCC activity of the molecule of interest may be assessed in vivo, e.g., in a animal model such as that disclosed in Clynes et al. Proc. Nat'l Acad. Sci. USA 95:652-656 (1998). Clq binding assays may also be carried out to confirm that the antibody is unable to bind Clq and hence lacks CDC activity. See, e.g., Clq and C3c binding ELISA in WO 2006/029879 and WO
2005/100402. To assess complement activation, a CDC assay may be performed (see, for example, Gazzano-Santoro et al., J. Immunol. Methods 202:163 (1996); Cragg, M.
S. etal., Blood 101:1045-1052 (2003); and Cragg, M. S. and M. J. Glennie, Blood 103:2738-(2004)). FcRn binding and in vivo clearance/half life determinations can also be performed using methods known in the art (see, e.g., Petkova, S. B. etal., Int'l.
Immunol. 18(12):1759-1769 (2006)).
[0085] In some embodiments, one or more amino acid modifications may be introduced into the Fc portion of the antibody provided herein in order to increase IgG
binding to the neonatal Fc receptor. In certain embodiments, the antibody comprises the following three mutations according to EU numbering: M252Y, 5254T, and T256E (the "YTE
mutation") (U.S. Pat. No. 8,697,650; see also Dall'Acqua et al., Journal of Biological Chemistry 281(33):23514-23524 (2006). In certain embodiments, the YTE mutation does not affect the ability of the antibody to bind to its cognate antigen. In certain embodiments, the YTE
mutation increases the antibody's serum half-life compared to the native (i.e., non-YTE
mutant) antibody. In some embodiments, the YTE mutation increases the serum half-life of the antibody by 3-fold compared to the native (i.e., non-YTE mutant) antibody.
In some embodiments, the YTE mutation increases the serum half-life of the antibody by 2-fold compared to the native (i.e., non-YTE mutant) antibody. In some embodiments, the YTE
mutation increases the serum half-life of the antibody by 4-fold compared to the native (i.e., non-YTE mutant) antibody. In some embodiments, the YTE mutation increases the serum half-life of the antibody by at least 5-fold compared to the native (i.e., non-YTE mutant) antibody. In some embodiments, the YTE mutation increases the serum half-life of the antibody by at least 10-fold compared to the native (i.e., non-YTE mutant) antibody. See, e.g., U.S. Pat. No. 8,697,650; see also Dall'Acqua et al., Journal of Biological Chemistry 281(33):23514-23524 (2006).
[0086] In certain embodiments, the YTE mutant provides a means to modulate antibody-dependent cell-mediated cytotoxicity (ADCC) activity of the antibody. In certain embodiments, the YTEO mutant provides a means to modulate ADCC activity of a humanized IgG antibody directed against a human antigen. See, e.g., U.S. Pat.
No. 8,697,650;
see also Dall'Acqua et al., Journal of Biological Chemistry 281(33):23514-23524 (2006).
In certain embodiments, the YTE mutant allows the simultaneous modulation of serum half-life, tissue distribution, and antibody activity (e.g., the ADCC activity of an IgG antibody).
See, e.g., U.S. Pat. No. 8,697,650; see also Dall'Acqua et al., Journal of Biological Chemistry 281(33):23514-23524 (2006).
[0087] Antibodies with reduced effector function include those with substitution of one or more of Fc region residues 238, 265, 269, 270, 297, 327 and 329 according to EU numbering (U.S. Pat. No. 6,737,056). Such Fc mutants include Fc mutants with substitutions at two or more of amino acid positions 265, 269, 270, 297 and 327 according to EU
numbering, including the so-called "DANA" Fc mutant with substitution of residues 265 and 297 to alanine according to EU numbering (i.e., D265A and N297A according to EU
numbering) (U.S. Pat. No. 7,332,581). In certain embodiments the Fc mutant comprises the following two amino acid substitutions: D265A and N297A. In certain embodiments the Fc mutant consists of the following two amino acid substitutions: D265A and N297A.
[0088] In certain embodiments, the proline at p05iti0n329 (EU numbering) (P329) of a wild-type human Fc region is substituted with glycine or arginine or an amino acid residue large enough to destroy the proline sandwich within the Fc/Fc.gamma. receptor interface, that is formed between the P329 of the Fc and tryptophane residues W87 and W110 of FcgRIII
(Sondermann et al.: Nature 406, 267-273 (20 Jul. 2000)). In a further embodiment, at least one further amino acid substitution in the Fc variant is 5228P, E233P, L234A, L235A, L235E, N297A, N297D, or P331S and still in another embodiment said at least one further amino acid substitution is L234A and L235A of the human IgG1 Fc region or 5228P and L235E of the human IgG4 Fc region, all according to EU numbering (U.S. Pat.
No. 8,969,526 which is incorporated by reference in its entirety).
[0089] In certain embodiments, a polypeptide comprises the Fc variant of a wild-type human IgG Fc region wherein the polypeptide has P329 of the human IgG Fc region substituted with glycine and wherein the Fc variant comprises at least two further amino acid substitutions at L234A and L235A of the human IgG1 Fc region or 5228P and L235E of the human IgG4 Fc region, and wherein the residues are numbered according to the EU numbering (U.S. Pat. No.
8,969,526 which is incorporated by reference in its entirety). In certain embodiments, the polypeptide comprising the P329G, L234A and L235A (EU numbering) substitutions exhibit a reduced affinity to the human Fc.gamma.RIIIA and Fc.gamma.RIIA, for down-modulation of ADCC to at least 20% of the ADCC induced by the polypeptide comprising the wildtype human IgG Fc region, and/or for down-modulation of ADCP (U.S. Pat. No.
8,969,526 which is incorporated by reference in its entirety).
[0090] In a specific embodiment the polypeptide comprising an Fc variant of a wildtype human Fc polypeptide comprises a triple mutation: an amino acid substitution at position Pro329, a L234A and a L235A mutation according to EU numbering (P329/LALA) (U.S.
Pat. No. 8,969,526 which is incorporated by reference in its entirety). In specific embodiments, the polypeptide comprises the following amino acid substitutions:
P329G, L234A, and L235A according to EU numbering.
[0091] Certain antibody variants with improved or diminished binding to FcRs are described.
(See, e.g., U.S. Pat. No. 6,737,056; WO 2004/056312, and Shields et al., J.
Biol. Chem. 9(2):
6591-6604 (2001).) [0092] In certain embodiments, an antibody variant comprises an Fc region with one or more amino acid substitutions which improve ADCC, e.g., substitutions at positions 298, 333, and/or 334 of the Fc region (EU numbering).
[0093] In some embodiments, alterations are made in the Fc region that result in altered (i. e., either improved or diminished) Clq binding and/or Complement Dependent Cytotoxicity (CDC), e.g., as described in U.S. Pat. No. 6,194,551, WO 99/51642, and Idusogie et al. J
Immunol. 164: 4178-4184 (2000).
[0094] Antibodies with increased half lives and improved binding to the neonatal Fc receptor (FcRn), which is responsible for the transfer of maternal IgGs to the fetus (Guyer et al., J.
Immunol. 117:587 (1976) and Kim et al., J. Immunol. 24:249 (1994)), are described in U52005/0014934A1 (Hinton et al.).
[0095] Those antibodies comprise an Fc region with one or more substitutions therein which improve binding of the Fc region to FcRn. Such Fc variants include those with substitutions at one or more of Fc region residues: 238, 256, 265, 272, 286, 303, 305, 307, 311, 312, 317, 340, 356, 360, 362, 376, 378, 380, 382, 413, 424 or 434, e.g., substitution of Fc region residue 434 (U.S. Pat. No. 7,371,826) according to EU numbering. See also Duncan &
Winter, Nature 322:738-40 (1988); U.S. Pat. No. 5,648,260; U.S. Pat. No.
5,624,821; and WO 94/29351 concerning other examples of Fc region variants.

[0096] An "Fab' fragment" contains one light chain and a portion of one heavy chain that contains the VH domain and the CH1 domain and also the region between the CH1 and CH2 domains, such that an interchain disulfide bond can be formed between the two heavy chains of two Fab' fragments to form an F(ab')2 molecule.
[0097] An "F(ab')2 fragment" contains two light chains and two heavy chains containing a portion of the constant region between the CH1 and CH2 domains, such that an interchain disulfide bond is formed between the two heavy chains. A F(ab')2 fragment thus is composed of two Fab' fragments that are held together by a disulfide bond between the two heavy chains.
[0098] The "Fv region" comprises the variable regions from both the heavy and light chains, but lacks the constant regions.
[0099] "Single chain antibodies" or "scFvs" are Fv molecules in which the heavy and light chain variable regions have been connected by a flexible linker to form a single polypeptide chain, which forms an antigen-binding region. scFvs are discussed in detail in International Patent Application Publication No. WO 88/01649 and United States Patent Nos.
4,946,778 and No. 5,260,203, the disclosures of which are incorporated by reference.
101001 A "domain antibody" or "single chain immunoglobulin" is an immunologically functional immunoglobulin fragment containing only the variable region of a heavy chain or the variable region of a light chain. Examples of domain antibodies include Nanobodies0. In some instances, two or more VH regions are covalently joined with a peptide linker to create a bivalent domain antibody. The two VH regions of a bivalent domain antibody may target the same or different antigens.
101011 A "bivalent antigen binding protein" or "bivalent antibody" comprises two antigen binding regions. In some instances, the two binding regions have the same antigen specificities. Bivalent antigen binding proteins and bivalent antibodies may be bispecific, see, infra.
[0102] A multispecific antigen binding protein" or "multispecific antibody" is one that targets more than one antigen or epitope.
[0103] A "bispecific," "dual-specific" or "bifunctional" antigen binding protein or antibody is a hybrid antigen binding protein or antibody, respectively, having two different antigen binding sites. Bispecific antigen binding proteins and antibodies are a species of multispecific antigen binding protein or multispecific antibody and may be produced by a variety of methods including, but not limited to, fusion of hybridomas or linking of Fab' fragments. See, e.g., Songsivilai and Lachmann, 1990, Clin. Exp. Immunol. 79:315-321; Kostelny et al., 1992, J. Immunol. 148:1547-1553. The two binding sites of a bispecific antigen binding protein or antibody will bind to two different epitopes, which may reside on the same or different protein targets.
[0104] The term "compete" when used in the context of antigen binding proteins (e.g., antibodies) means competition between antigen binding proteins is determined by an assay in which the antigen binding protein (e.g., antibody or immunologically functional fragment thereof) under test prevents or inhibits specific binding of a reference antigen binding protein to a common antigen (e.g., GIPR or a fragment thereof). Numerous types of competitive binding assays can be used, for example: solid phase direct or indirect radioimmunoassay (RIA), solid phase direct or indirect enzyme immunoassay (ETA), sandwich competition assay (see, e.g., Stahli et al., 1983, Methods in Enzymology 9:242-253); solid phase direct biotin-avidin ETA (see, e.g., Kirkland et al., 1986, J. Immunol. 137:3614-3619) solid phase direct labeled assay, solid phase direct labeled sandwich assay (see, e.g., Harlow and Lane, 1988, Antibodies, A Laboratory Manual, Cold Spring Harbor Press); solid phase direct label RIA using 1-125 label (see, e.g., Morel et al., 1988, Molec. Immunol. 25:7-15); solid phase direct biotin-avidin ETA (see, e.g., Cheung, et al., 1990, Virology 176:546-552); and direct labeled RIA (Moldenhauer et al., 1990, Scand. J. Immunol. 32:77-82).
Typically, such an assay involves the use of purified antigen bound to a solid surface or cells bearing either of these, an unlabeled test antigen binding protein and a labeled reference antigen binding protein. Competitive inhibition is measured by determining the amount of label bound to the solid surface or cells in the presence of the test antigen binding protein.
Usually the test antigen binding protein is present in excess. Additional details regarding methods for determining competitive binding are provided in the examples herein. Usually, when a competing antigen binding protein is present in excess, it will inhibit specific binding of a reference antigen binding protein to a common antigen by at least 40%, 45%, 50%, 55%, 60%, 65%, 70% or 75%. In some instances, binding is inhibited by at least 80%, 85%, 90%, 95%, or 97% or more.
[0105] The term "antigen" refers to a molecule or a portion of a molecule capable of being bound by a selective binding agent, such as an antigen binding protein (including, e.g., an antibody), and additionally capable of being used in an animal to produce antibodies capable of binding to that antigen. An antigen may possess one or more epitopes that are capable of interacting with different antigen binding proteins, e.g., antibodies.
[0106] The term "epitope" is the portion of a molecule that is bound by an antigen binding protein (for example, an antibody). The term includes any determinant capable of specifically binding to an antigen binding protein, such as an antibody. An epitope can be contiguous or non-contiguous (discontinuous) (e.g., in a polypeptide, amino acid residues that are not contiguous to one another in the polypeptide sequence but that within in context of the molecule are bound by the antigen binding protein). A conformational epitope is an epitope that exists within the conformation of an active protein but is not present in a denatured protein. In certain embodiments, epitopes may be mimetic in that they comprise a three dimensional structure that is similar to an epitope used to generate the antigen binding protein, yet comprise none or only some of the amino acid residues found in that epitope used to generate the antigen binding protein. Most often, epitopes reside on proteins, but in some instances may reside on other kinds of molecules, such as nucleic acids.
Epitope determinants may include chemically active surface groupings of molecules such as amino acids, sugar side chains, phosphoryl or sulfonyl groups, and may have specific three dimensional structural characteristics, and/or specific charge characteristics. Generally, antigen binding proteins specific for a particular target antigen will preferentially recognize an epitope on the target antigen in a complex mixture of proteins and/or macromolecules.
[0107] As used herein, "substantially pure" means that the described species of molecule is the predominant species present, that is, on a molar basis it is more abundant than any other individual species in the same mixture. In certain embodiments, a substantially pure molecule is a composition wherein the object species comprises at least 50% (on a molar basis) of all macromolecular species present. In other embodiments, a substantially pure composition will comprise at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% of all macromolecular species present in the composition. In other embodiments, the object species is purified to essential homogeneity wherein contaminating species cannot be detected in the composition by conventional detection methods and thus the composition consists of a single detectable macromolecular species.
[0108] The term "treating" refers to any indicia of success in the treatment or amelioration of an injury, pathology or condition, including any objective or subjective parameter such as abatement; remission; diminishing of symptoms or making the injury, pathology or condition more tolerable to the patient; slowing in the rate of degeneration or decline;
making the final point of degeneration less debilitating; improving a patient's physical or mental well-being.
The treatment or amelioration of symptoms can be based on objective or subjective parameters; including the results of a physical examination, neuropsychiatric exams, and/or a psychiatric evaluation. For example, certain methods presented herein successfully treat cardiovascular disease such as atherosclerosis by decreasing the incidence of cardiovascular disease, causing remission of cardiovascular disease and/or ameliorating a symptom associated with cardiovascular disease.
[0109] An "effective amount" is generally an amount sufficient to reduce the severity and/or frequency of symptoms, eliminate the symptoms and/or underlying cause, prevent the occurrence of symptoms and/or their underlying cause, and/or improve or remediate the damage that results from or is associated with the disease state (e.g., diabetes, obesity, dyslipidemia, elevated glucose levels, elevated insulin levels or diabetic nephropathy. In some embodiments, the effective amount is a therapeutically effective amount or a prophylactically effective amount. A "therapeutically effective amount" is an amount sufficient to remedy a disease state (e.g. atherosclerosis) or symptoms, particularly a state or symptoms associated with the disease state, or otherwise prevent, hinder, retard or reverse the progression of the disease state or any other undesirable symptom associated with the disease in any way whatsoever. A "prophylactically effective amount" is an amount of a pharmaceutical composition that, when administered to a subject, will have the intended prophylactic effect, e.g., preventing or delaying the onset (or reoccurrence) of the disease state, or reducing the likelihood of the onset (or reoccurrence) of the disease state or associated symptoms. The full therapeutic or prophylactic effect does not necessarily occur by administration of one dose, and may occur only after administration of a series of doses.
Thus, a therapeutically or prophylactically effective amount may be administered in one or more administrations.
[0110] The terms "therapeutically effective dose" and "therapeutically effective amount," as used herein, means an amount of a GIPR binding protein that elicits a biological or medicinal response in a tissue system, animal, or human being sought by a researcher, physician, or other clinician, which includes alleviation or amelioration of the symptoms of the disease or disorder being treated, i.e., an amount of a GIPR binding protein that supports an observable level of one or more desired biological or medicinal response, for example lowering blood glucose, insulin, triglyceride, or cholesterol levels; reducing body weight;
or improving glucose tolerance, energy expenditure, or insulin sensitivity.
[0111] The term "polynucleotide" or "nucleic acid" includes both single-stranded and double-stranded nucleotide polymers. The nucleotides comprising the polynucleotide can be ribonucleotides or deoxyribonucleotides or a modified form of either type of nucleotide. The modifications include base modifications such as bromouridine and inosine derivatives, ribose modifications such as 2',3'-dideoxyribose, and intemucleotide linkage modifications such as phosphorothioate, phosphorodithioate, phosphoroselenoate, phosphorodiselenoate, phosphoroanilothioate, phoshoraniladate and phosphoroamidate.
[0112] The term "oligonucleotide" means a polynucleotide comprising 200 or fewer nucleotides. In some embodiments, oligonucleotides are 10 to 60 bases in length. In other embodiments, oligonucleotides are 12, 13, 14, 15, 16, 17, 18, 19, or 20 to 40 nucleotides in length. Oligonucleotides may be single stranded or double stranded, e.g., for use in the construction of a mutant gene. Oligonucleotides may be sense or antisense oligonucleotides.
An oligonucleotide can include a label, including a radiolabel, a fluorescent label, a hapten or an antigenic label, for detection assays. Oligonucleotides may be used, for example, as PCR
primers, cloning primers or hybridization probes.
[0113] An "isolated nucleic acid molecule" means a DNA or RNA of genomic, mRNA, cDNA, or synthetic origin or some combination thereof which is not associated with all or a portion of a polynucleotide in which the isolated polynucleotide is found in nature, or is linked to a polynucleotide to which it is not linked in nature. For purposes of this disclosure, it should be understood that "a nucleic acid molecule comprising" a particular nucleotide sequence does not encompass intact chromosomes. Isolated nucleic acid molecules "comprising" specified nucleic acid sequences may include, in addition to the specified sequences, coding sequences for up to ten or even up to twenty other proteins or portions thereof, or may include operably linked regulatory sequences that control expression of the coding region of the recited nucleic acid sequences, and/or may include vector sequences.
[0114] Unless specified otherwise, the left-hand end of any single-stranded polynucleotide sequence discussed herein is the 5' end; the left-hand direction of double-stranded polynucleotide sequences is referred to as the 5' direction. The direction of 5' to 3' addition of nascent RNA transcripts is referred to as the transcription direction;
sequence regions on the DNA strand having the same sequence as the RNA transcript that are 5' to the 5' end of the RNA transcript are referred to as "upstream sequences;" sequence regions on the DNA strand having the same sequence as the RNA transcript that are 3' to the 3' end of the RNA transcript are referred to as "downstream sequences."
[0115] The term "control sequence" refers to a polynucleotide sequence that can affect the expression and processing of coding sequences to which it is ligated. The nature of such control sequences may depend upon the host organism. In particular embodiments, control sequences for prokaryotes may include a promoter, a ribosomal binding site, and a transcription termination sequence. For example, control sequences for eukaryotes may include promoters comprising one or a plurality of recognition sites for transcription factors, transcription enhancer sequences, and transcription termination sequences.
"Control sequences" can include leader sequences and/or fusion partner sequences.
[0116] The term "vector" means any molecule or entity (e.g., nucleic acid, plasmid, bacteriophage or virus) used to transfer protein coding information into a host cell.
[0117] The term "expression vector" or "expression construct" refers to a vector that is suitable for transformation of a host cell and contains nucleic acid sequences that direct and/or control (in conjunction with the host cell) expression of one or more heterologous coding regions operatively linked thereto. An expression construct may include, but is not limited to, sequences that affect or control transcription, translation, and, if introns are present, affect RNA splicing of a coding region operably linked thereto.
[0118] As used herein, "operably linked" means that the components to which the term is applied are in a relationship that allows them to carry out their inherent functions under suitable conditions. For example, a control sequence in a vector that is "operably linked" to a protein coding sequence is ligated thereto so that expression of the protein coding sequence is achieved under conditions compatible with the transcriptional activity of the control sequences.
[0119] The term "host cell" means a cell that has been transformed with a nucleic acid sequence and thereby expresses a gene of interest. The term includes the progeny of the parent cell, whether or not the progeny is identical in morphology or in genetic make-up to the original parent cell, so long as the gene of interest is present.
[0120] The terms "polypeptide" or "protein" are used interchangeably herein to refer to a polymer of amino acid residues. The terms also apply to amino acid polymers in which one or more amino acid residues is an analog or mimetic of a corresponding naturally occurring amino acid, as well as to naturally occurring amino acid polymers. The terms can also encompass amino acid polymers that have been modified, e.g., by the addition of carbohydrate residues to form glycoproteins, or phosphorylated. Polypeptides and proteins can be produced by a naturally-occurring and non-recombinant cell; or it is produced by a genetically-engineered or recombinant cell, and comprise molecules having the amino acid sequence of the native protein, or molecules having deletions from, additions to, and/or substitutions of one or more amino acids of the native sequence. The terms "polypeptide" and "protein" specifically encompass GIPR antigen binding proteins, antibodies, or sequences that have deletions from, additions to, and/or substitutions of one or more amino acids of an antigen-binding protein. The term "polypeptide fragment" refers to a polypeptide that has an amino-terminal deletion, a carboxyl-terminal deletion, and/or an internal deletion as compared with the full-length protein. Such fragments may also contain modified amino acids as compared with the full-length protein. In certain embodiments, fragments are about five to 500 amino acids long. For example, fragments may be at least 5, 6, 8, 10, 14, 20, 50, 70, 100, 110, 150, 200, 250, 300, 350, 400, or 450 amino acids long. Useful polypeptide fragments include immunologically functional fragments of antibodies, including binding domains.
[0121] The term "isolated protein" means that a subject protein (1) is free of at least some other proteins with which it would normally be found, (2) is essentially free of other proteins from the same source, e.g., from the same species, (3) is expressed by a cell from a different species, (4) has been separated from at least about 50 percent of polynucleotides, lipids, carbohydrates, or other materials with which it is associated in nature, (5) is operably associated (by covalent or noncovalent interaction) with a polypeptide with which it is not associated in nature, or (6) does not occur in nature. Typically, an "isolated protein"
constitutes at least about 5%, at least about 10%, at least about 25%, or at least about 50% of a given sample. Genomic DNA, cDNA, mRNA or other RNA, of synthetic origin, or any combination thereof may encode such an isolated protein. Preferably, the isolated protein is substantially free from proteins or polypeptides or other contaminants that are found in its natural environment that would interfere with its therapeutic, diagnostic, prophylactic, research or other use.
[0122] A "variant" of a polypeptide (e.g., an antigen binding protein such as an antibody) comprises an amino acid sequence wherein one or more amino acid residues are inserted into, deleted from and/or substituted into the amino acid sequence relative to another polypeptide sequence. Variants include fusion proteins.
[0123] A "derivative" of a polypeptide is a polypeptide (e.g., an antigen binding protein such as an antibody) that has been chemically modified in some manner distinct from insertion, deletion, or substitution variants, e.g., via conjugation to another chemical moiety.
[0124] The term "naturally occurring" as used throughout the specification in connection with biological materials such as polypeptides, nucleic acids, host cells, and the like, refers to materials which are found in nature.
[0125] A "subject" or "patient" as used herein can be any mammal. In a typical embodiment, the subject or patient is a human.
[0126] As disclosed herein, a GIPR polypeptide described by the instant disclosure can be engineered and/or produced using standard molecular biology methodology. In various examples, a nucleic acid sequence encoding a GIPR, which can comprise all or a portion of SEQ ID NOs: 1203, 1203 or 1205, can be isolated and/or amplified from genomic DNA, or cDNA using appropriate oligonucleotide primers. Primers can be designed based on the nucleic and amino acid sequences provided herein according to standard (RT)-PCR
amplification techniques. The amplified GIPR nucleic acid can then be cloned into a suitable vector and characterized by DNA sequence analysis.
[0127] Oligonucleotides for use as probes in isolating or amplifying all or a portion of the GIPR sequences provided herein can be designed and generated using standard synthetic techniques, e.g., automated DNA synthesis apparatus, or can be isolated from a longer sequence of DNA.
[0128] The 466 amino acid sequence of human GIPR is (Volz et al., FEBS Lett.
373:23-29 (1995); NCBI Reference Sequence: NP 0001555):
[0129] MTTSPILQLL LRLSLCGLLL QRAETGSKGQ TAGELYQRWE RYRRECQETL
AAAEPPSGLA CNGSFDMYVC WDYAAPNATA RASCPWYLPW HHHVAAGFVL
RQCGSDGQWG LWRDHTQCEN PEKNEAFLDQ RLILERLQVM YTVGYSLSLA
TLLLALLILS LFRRLHCTRN YIHINLFTSF MLRAAAILSR DRLLPRPGPY
LGDQALALWN QALAACRTAQ IVTQYCVGAN YTWLLVEGVY LHSLLVLVGG
SEEGHFRYYL LLGWGAPALF VIPWVIVRYL YENTQCWERN EVKAIWWIIR
TPILMTILIN FLIFIRILGI LLSKLRTRQM RCRDYRLRLA RSTLTLVPLL
GVHEVVFAPV TEEQARGALR FAKLGFEIFL SSFQGFLVSV LYCFINKEVQ
SEIRRGWHHC RLRRSLGEEQ RQLPERAFRA LPSGSGPGEV PTSRGLSSGT
LPGPGNEASR ELESYC (SEQIDNO: 1201) [0130] and is encoded by the DNA sequence (NCBI Reference Sequence: NM
000164):
[0131] ggcagcggtg gcaggggctg caggagcaag tgaccaggag caggactggg gacaggcctg atcgcccctg cacgaaccag acccttcgcc gccctcacga tgactacctc tccgatcctg cagctgctgc tgcggctctc actgtgcggg ctgctgctcc agagggcgga gacaggctct aaggggcaga cggcggggga gctgtaccag cgctgggaac ggtaccgcag ggagtgccag gagaccttgg cagccgcgga accgccttca ggcctcgcct gtaacgggtc cttcgatatg tacgtctgct gggactatgc tgcacccaat gccactgccc gtgcgtcctg cccctggtac ctgccctggc accaccatgt ggctgcaggt ttcgtcctcc gccagtgtgg cagtgatggc caatggggac tttggagaga ccatacacaa tgtgagaacc cagagaagaa tgaggccttt ctggaccaaa ggctcatctt ggagcggttg caggtcatgt acactgtcgg ctactccctg tctctcgcca cactgctgct agccctgctc atcttgagtt tgttcaggcg gctacattgc actagaaact atatccacat caacctgttc acgtctttca tgctgcgagc tgcggccatt ctcagccgag accgtctgct acctcgacct ggcccctacc ttggggacca ggcccttgcg ctgtggaacc aggccctcgc tgcctgccgc acggcccaga tcgtgaccca gtactgcgtg ggtgccaact acacgtggct gctggtggag ggcgtctacc tgcacagtct cctggtgctc gtgggaggct ccgaggaggg ccacttccgc tactacctgc tcctcggctg gggggccccc gcgcttttcg tcattccctg ggtgatcgtc aggtacctgt acgagaacac gcagtgctgg gagcgcaacg aagtcaaggc catttggtgg attatacgga cccccatcct catgaccatc ttgattaatt tcctcatttt tatccgcatt cttggcattc tcctgtccaa gctgaggaca cggcaaatgc gctgccggga ttaccggctg aggctggctc gctccacgct gacgctggtg cccctgctgg gtgtccacga ggtggtgttt gctcccgtga cagaggaaca ggcccggggc gccctgcgct tcgccaagct cggctttgag atcttcctca gctccttcca gggcttcctg gtcagcgtcc tctactgctt catcaacaag gaggtgcagt cggagatccg ccgtggctgg caccactgcc gcctgcgccg cagcctgggc gaggagcaac gccagctccc ggagcgcgcc ttccgggccc tgccctccgg ctccggcccg ggcgaggtcc ccaccagccg cggcttgtcc tcggggaccc tcccagggcc tgggaatgag gccagccggg agttggaaag ttactgctag ggggcgggat ccccgtgtct gttcagttag catggattta ttgagtgcca actgcgtgcc aggcccagta cggaggacgc tggggaaatg gtgaaggaaa cagaaaaaag gtccctgccc ttctggagat gacaactgag tggggaaaac agaccgtgaa cacaaaacat caagttccac acacgctatg gaatggttat gaagggaagc gagaaggggg cctagggtgg tctgggaggc gtctccaagg aggtgacact taagccatcc ccgaaagagg tgaaagagat cactttgggg agagctggag aacaggattc taggcggaag cgatagcata ggcaaaggcc cttgggcagg aaggcgctca gccttggctg gagtagaatt aagtcagagc caacaggtgg ggagagacag agaagtgggc aggggcaccc aagttgggat ttcatttcag gtgcattgga gattcttagg agtgtctctt gggggtaata ttttattttt taaaaaatga ggat (SEQIDNO: 1202).
[0132] A 430 amino acid isoform of human GIPR (isoform X1), predicted by automated computational analysis, has the sequence (NCBI Reference Sequence XP
005258790):
[0133] MTTSPILQLL LRLSLCGLLL QRAETGSKGQ TAGELYQRWE RYRRECQETL
AAAEPPSVAA GFVLRQCGSD GQWGLWRDHT QCENPEKNEA FLDQRLILER
LQVMYTVGYS LSLATLLLAL LILSLFRRLH CTRNYIHINL FTSFMLRAAA

ILSRDRLLPR PGPYLGDQAL ALWNQALAAC RTAQIVTQYC VGANYTWLLV
EGVYLHSLLV LVGGSEEGHF RYYLLLGWGA PALFVIPWVI VRYLYENTQC
WERNEVKAIW WIIRTPILMT ILINFLIFIR ILGILLSKLR TRQMRCRDYR
LRLARSTLTL VPLLGVHEVV FAPVTEEQAR GALRFAKLGF EIFLSSFQGF
LVSVLYCFIN KEVQSEIRRG WHHCRLRRSL GEEQRQLPER AFRALPSGSG
PGEVPTSRGL SSGTLPGPGN EASRELESYC(SEQIDNO: 1203) [0134] and is encoded by the DNA sequence:
[0135] atgaccacca gcccgattct gcagctgctg ctgcgcctga gcctgtgcgg cctgctgctg cagcgcgcgg aaaccggcag caaaggccag accgcgggcg aactgtatca gcgctgggaa cgctatcgcc gcgaatgcca ggaaaccctg gcggcggcgg aaccgccgag cgtggcggcg ggctttgtgc tgcgccagtg cggcagcgat ggccagtggg gcctgtggcg cgatcatacc cagtgcgaaa acccggaaaa aaacgaagcg tttctggatc agcgcctgat tctggaacgc ctgcaggtga tgtataccgt gggctatagc ctgagcctgg cgaccctgct gctggcgctg ctgattctga gcctgtttcg ccgcctgcat tgcacccgca actatattca tattaacctg tttaccagct ttatgctgcg cgcggcggcg attctgagcc gcgatcgcct gctgccgcgc ccgggcccgt atctgggcga tcaggcgctg gcgctgtgga accaggcgct ggcggcgtgc cgcaccgcgc agattgtgac ccagtattgc gtgggcgcga actatacctg gctgctggtg gaaggcgtgt atctgcatag cctgctggtg ctggtgggcg gcagcgaaga aggccatttt cgctattatc tgctgctggg ctggggcgcg ccggcgctgt ttgtgattcc gtgggtgatt gtgcgctatc tgtatgaaaa cacccagtgc tgggaacgca acgaagtgaa agcgatttgg tggattattc gcaccccgat tctgatgacc attctgatta actttctgat ttttattcgc attctgggca ttctgctgag caaactgcgc acccgccaga tgcgctgccg cgattatcgc ctgcgcctgg cgcgcagcac cctgaccctg gtgccgctgc tgggcgtgca tgaagtggtg tttgcgccgg tgaccgaaga acaggcgcgc ggcgcgctgc gctttgcgaa actgggcttt gaaatttttc tgagcagctt tcagggcttt ctggtgagcg tgctgtattg ctttattaac aaagaagtgc agagcgaaat tcgccgcggc tggcatcatt gccgcctgcg ccgcagcctg ggcgaagaac agcgccagct gccggaacgc gcgtttcgcg cgctgccgag cggcagcggc ccgggcgaag tgccgaccag ccgcggcctg agcagcggca ccctgccggg cccgggcaac gaagcgagcc gcgaactgga aagctattgc(SEQIDNO: 1204).

[0136] A 493 amino acid isoform of human GIPR, produced by alternative splicing, has the sequence (Gremlich et al., Diabetes 44:1202-8 (1995); UniProtKB Sequence Identifier:
P48546-2):

AAAEPPSGLA CNGSFDMYVC WDYAAPNATA RASCPWYLPW HHHVAAGFVL
RQCGSDGQWG LWRDHTQCEN PEKNEAFLDQ RLILERLQVM YTVGYSLSLA
TLLLALLILS LFRRLHCTRN YIHINLFTSF MLRAAAILSR DRLLPRPGPY
LGDQALALWN QALAACRTAQ IVTQYCVGAN YTWLLVEGVY LHSLLVLVGG
SEEGHFRYYL LLGWGAPALF VIPWVIVRYL YENTQCWERN EVKAIWWIIR
TPILMTILIN FLIFIRILGI LLSKLRTRQM RCRDYRLRLA RSTLTLVPLL
GVHEVVFAPV TEEQARGALR FAKLGFEIFL SSFQGFLVSV LYCFINKEVG
RDPAAAPALW RRRGTAPPLS AIVSQVQSEI RRGWHHCRLR RSLGEEQRQL
PERAFRALPS GSGPGEVPTS RGLSSGTLPG PGNEASRELE SYC(SEQIDNO: 1205) [0138] and is encoded by the DNA sequence:
[0139] atgaccacca gcccgattct gcagctgctg ctgcgcctga gcctgtgcgg cctgctgctg cagcgcgcgg aaaccggcag caaaggccag accgcgggcg aactgtatca gcgctgggaa cgctatcgcc gcgaatgcca ggaaaccctg gcggcggcgg aaccgccgag cggcctggcg tgcaacggca gctttgatat gtatgtgtgc tgggattatg cggcgccgaa cgcgaccgcg cgcgcgagct gcccgtggta tctgccgtgg catcatcatg tggcggcggg ctttgtgctg cgccagtgcg gcagcgatgg ccagtggggc ctgtggcgcg atcataccca gtgcgaaaac ccggaaaaaa acgaagcgtt tctggatcag cgcctgattc tggaacgcct gcaggtgatg tataccgtgg gctatagcct gagcctggcg accctgctgc tggcgctgct gattctgagc ctgtttcgcc gcctgcattg cacccgcaac tatattcata ttaacctgtt taccagcttt atgctgcgcg cggcggcgat tctgagccgc gatcgcctgc tgccgcgccc gggcccgtat ctgggcgatc aggcgctggc gctgtggaac caggcgctgg cggcgtgccg caccgcgcag attgtgaccc agtattgcgt gggcgcgaac tatacctggc tgctggtgga aggcgtgtat ctgcatagcc tgctggtgct ggtgggcggc agcgaagaag gccattttcg ctattatctg ctgctgggct ggggcgcgcc ggcgctgttt gtgattccgt gggtgattgt gcgctatctg tatgaaaaca cccagtgctg ggaacgcaac gaagtgaaag cgatttggtg gattattcgc accccgattc tgatgaccat tctgattaac tttctgattt ttattcgcat tctgggcatt ctgctgagca aactgcgcac ccgccagatg cgctgccgcg attatcgcct gcgcctggcg cgcagcaccc tgaccctggt gccgctgctg ggcgtgcatg aagtggtgtt tgcgccggtg accgaagaac aggcgcgcgg cgcgctgcgc tttgcgaaac tgggctttga aatttttctg agcagctttc agggctttct ggtgagcgtg ctgtattgct ttattaacaa agaagtgggc cgcgatccgg cggcggcgcc ggcgctgtgg cgccgccgcg gcaccgcgcc gccgctgagc gcgattgtga gccaggtgca gagcgaaatt cgccgcggct ggcatcattg ccgcctgcgc cgcagcctgg gcgaagaaca gcgccagctg ccggaacgcg cgtttcgcgc gctgccgagc ggcagcggcc cgggcgaagt gccgaccagc cgcggcctga gcagcggcac cctgccgggc ccgggcaacg aagcgagccg cgaactggaa agctattgct aa (SEQ ID NO: 1206) [0140] The 460 amino acid sequence of murine GIPR is (NCBI Reference Sequence:
NP 001074284; uniprotKB/Swiss-Prot Q0P543-1); see Vassilatis et al., PNAS USA
2003, 100:4903-4908.
[0141] MPLRLLLLLL WLWGLQWAET DSEGQTTTGE LYQRWEHYGQ ECQKMLETTE
PPSGLACNGS FDMYACWNYT AANTTARVSC PWYLPWFRQV SAGFVFRQCG
SDGQWGSWRD HTQCENPEKN GAFQDQTLIL ERLQIMYTVG YSLSLTTLLL
ALLILSLFRR LHCTRNYIHM NLFTSFMLRA AAILTRDQLL PPLGPYTGDQ
APTPWNQALA ACRTAQIMTQ YCVGANYTWL LVEGVYLHHL LVIVGRSEKG
HFRCYLLLGW GAPALFVIPW VIVRYLRENT QCWERNEVKA IWWIIRTPIL
ITILINFLIF IRILGILVSK LRTRQMRCPD YRLRLARSTL TLVPLLGVHE
VVFAPVTEEQ VEGSLRFAKL AFEIFLSSFQ GFLVSVLYCFINKEVQSEIRQ
GWRHRRLRLS LQEQRPRPHQ ELAPRAVPLS SACREAAVGN ALPSGMLHVP
GDEVLESYC (SEQ ID NO: 1207) [0142] and is encoded by the DNA sequence (NCBI Reference Sequence: NM
001080815):
[0143] atgccgctgc gcctgctgct gctgctgctg tggctgtggg gcctgcagtg ggcggaaacc gatagcgaag gccagaccac caccggcgaa ctgtatcagc gctgggaaca ttatggccag gaatgccaga aaatgctgga aaccaccgaa ccgccgagcg gcctggcgtg caacggcagc tttgatatgt atgcgtgctg gaactatacc gcggcgaaca ccaccgcgcg cgtgagctgc ccgtggtatc tgccgtggtt tcgccaggtg agcgcgggct ttgtgtttcg ccagtgcggc agcgatggcc agtggggcag ctggcgcgat catacccagt gcgaaaaccc ggaaaaaaac ggcgcgtttc aggatcagac cctgattctg gaacgcctgc agattatgta taccgtgggc tatagcctga gcctgaccac cctgctgctg gcgctgctga ttctgagcct gtttcgccgc ctgcattgca cccgcaacta tattcatatg aacctgttta ccagctttat gctgcgcgcg gcggcgattc tgacccgcga tcagctgctg ccgccgctgg gcccgtatac cggcgatcag gcgccgaccc cgtggaacca ggcgctggcg gcgtgccgca ccgcgcagat tatgacccag tattgcgtgg gcgcgaacta tacctggctg ctggtggaag gcgtgtatct gcatcatctg ctggtgattg tgggccgcag cgaaaaaggc cattttcgct gctatctgct gctgggctgg ggcgcgccgg cgctgtttgt gattccgtgg gtgattgtgc gctatctgcg cgaaaacacc cagtgctggg aacgcaacga agtgaaagcg atttggtgga ttattcgcac cccgattctg attaccattc tgattaactt tctgattttt attcgcattc tgggcattct ggtgagcaaa ctgcgcaccc gccagatgcg ctgcccggat tatcgcctgc gcctggcgcg cagcaccctg accctggtgc cgctgctggg cgtgcatgaa gtggtgtttg cgccggtgac cgaagaacag gtggaaggca gcctgcgctt tgcgaaactg gcgtttgaaa tttttctgag cagctttcag ggctttctgg tgagcgtgct gtattgcttt attaacaaag aagtgcagag cgaaattcgc cagggctggc gccatcgccg cctgcgcctg agcctgcagg aacagcgccc gcgcccgcat caggaactgg cgccgcgcgc ggtgccgctg agcagcgcgt gccgcgaagc ggcggtgggc aacgcgctgc cgagcggcat gctgcatgtg ccgggcgatg aagtgctgga aagctattgc taa (SEQ ID NO: 1208) [0144] A 230 amino acid isoform of murine GIPR, produced by alternative splicing, has the sequence (Gerhard et al., Genome Res, 14:2121-2127 (2004); NCBI Reference Sequence:
AAI20674):
[0145] MPLRLLLLLL WLWGLQWAET DSEGQTTTGE LYQRWEHYGQ ECQKMLETTE
PPSGLACNGS FDMYACWNYT AANTTARVSC PWYLPWFRQV SAGFVFRQCG
SDGQWGSWRD HTQCENPEKN GAFQDQTLIL ERLQIMYTVG YSLSLTTLLL
ALLILSLFRR LHCTRNYIHM NLFTSFMLRA AAILTRDQLL PPLGPYTGDQ
APTPWNQVLH RLLPGGTKTF PIYFRTFPHH(SEQIDNO: 1209) [0146] and is encoded by the DNA sequence:
[0147] atgccgctgc gcctgctgct gctgctgctg tggctgtggg gcctgcagtg ggcggaaacc gatagcgaag gccagaccac caccggcgaa ctgtatcagc gctgggaaca ttatggccag gaatgccaga aaatgctgga aaccaccgaa ccgccgagcg gcctggcgtg caacggcagc tttgatatgt atgcgtgctg gaactatacc gcggcgaaca ccaccgcgcg cgtgagctgc ccgtggtatc tgccgtggtt tcgccaggtg agcgcgggct ttgtgtttcg ccagtgcggc agcgatggcc agtggggcag ctggcgcgat catacccagt gcgaaaaccc ggaaaaaaac ggcgcgtttc aggatcagac cctgattctg gaacgcctgc agattatgta taccgtgggc tatagcctga gcctgaccac cctgctgctg gcgctgctga ttctgagcct gtttcgccgc ctgcattgca cccgcaacta tattcatatg aacctgttta ccagctttat gctgcgcgcg gcggcgattc tgacccgcga tcagctgctg ccgccgctgg gcccgtatac cggcgatcag gcgccgaccc cgtggaacca ggtgctgcat cgcctgctgc cgggcggcac caaaaccttt ccgatttatt ttcgcacctt tccgcatcat taa(SEQIDNO: 1210).
[0148] As stated herein, the term "GIPR polypeptide" encompasses naturally occurring GIPR
polypeptide sequences, e.g., human amino acid sequences SEQ ID NOs: 1201, 1203 or 1205.
The term "GIPR polypeptide," however, also encompasses polypeptides comprising an amino acid sequence that differs from the amino acid sequence of a naturally occurring GIPR
polypeptide sequence, e.g., SEQ ID NOs: 1201, 1203 or 1205, by one or more amino acids, such that the sequence is at least 85% identical to SEQ ID NOs: 1201, 1203 or 1205. GIPR
polypeptides can be generated by introducing one or more amino acid substitutions, either conservative or non-conservative and using naturally or non-naturally occurring amino acids, at particular positions of the GIPR polypeptide.
[0149] A "conservative amino acid substitution" can involve a substitution of a native amino acid residue (i.e., a residue found in a given position of the wild-type GIPR
polypeptide sequence) with a nonnative residue (i.e., a residue that is not found in a given position of the wild-type GIPR polypeptide sequence) such that there is little or no effect on the polarity or charge of the amino acid residue at that position. Conservative amino acid substitutions also encompass non-naturally occurring amino acid residues that are typically incorporated by chemical peptide synthesis rather than by synthesis in biological systems.
These include peptidomimetics, and other reversed or inverted forms of amino acid moieties.
[0150] Naturally occurring residues can be divided into classes based on common side chain properties:
[0151] (1) hydrophobic: norleucine, Met, Ala, Val, Leu, Ile;
[0152] (2) neutral hydrophilic: Cys, Ser, Thr;
[0153] (3) acidic: Asp, Glu;
[0154] (4) basic: Asn, Gln, His, Lys, Arg;
[0155] (5) residues that influence chain orientation: Gly, Pro; and [0156] (6) aromatic: Trp, Tyr, Phe.
[0157] Additional groups of amino acids can also be formulated using the principles described in, e.g., Creighton (1984) PROTEINS: STRUCTURE AND MOLECULAR

PROPERTIES (2d Ed. 1993), W.H. Freeman and Company. In some instances it can be useful to further characterize substitutions based on two or more of such features (e.g., substitution with a "small polar" residue, such as a Thr residue, can represent a highly conservative substitution in an appropriate context).
[0158] Conservative substitutions can involve the exchange of a member of one of these classes for another member of the same class. Non-conservative substitutions can involve the exchange of a member of one of these classes for a member from another class.
[0159] Synthetic, rare, or modified amino acid residues having known similar physiochemical properties to those of an above-described grouping can be used as a "conservative" substitute for a particular amino acid residue in a sequence.
For example, a D-Arg residue may serve as a substitute for a typical L-Arg residue. It also can be the case that a particular substitution can be described in terms of two or more of the above described classes (e.g., a substitution with a small and hydrophobic residue means substituting one amino acid with a residue(s) that is found in both of the above-described classes or other synthetic, rare, or modified residues that are known in the art to have similar physiochemical properties to such residues meeting both definitions).
[0160] Nucleic acid sequences encoding a GIPR polypeptide provided herein, including those degenerate to SEQ ID NOs: 1201, 1203 or 1205, and those encoding polypeptide variants of SEQ ID NOs: 1201, 1203 or 1205 form other aspects of the instant disclosure.
[0161] In order to express the GIPR nucleic acid sequences provided herein, the appropriate coding sequences, e.g., SEQ ID NOs: 1201, 1203 or 1205, can be cloned into a suitable vector and after introduction in a suitable host, the sequence can be expressed to produce the encoded polypeptide according to standard cloning and expression techniques, which are known in the art (e.g., as described in Sambrook, J., Fritsh, E. F., and Maniatis, T. Molecular Cloning: A Laboratory Manual 2nd, ed., Cold Spring Harbor Laboratory, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1989). The invention also relates to such vectors comprising a nucleic acid sequence according to the invention.
[0162] A "vector" refers to a delivery vehicle that (a) promotes the expression of a polypeptide-encoding nucleic acid sequence; (b) promotes the production of the polypeptide therefrom; (c) promotes the transfection/transformation of target cells therewith; (d) promotes the replication of the nucleic acid sequence; (e) promotes stability of the nucleic acid; (0 promotes detection of the nucleic acid and/or transformed/transfected cells;
and/or (g) otherwise imparts advantageous biological and/or physiochemical function to the polypeptide-encoding nucleic acid. A vector can be any suitable vector, including chromosomal, non-chromosomal, and synthetic nucleic acid vectors (a nucleic acid sequence comprising a suitable set of expression control elements). Examples of such vectors include derivatives of SV40, bacterial plasmids, phage DNA, baculovirus, yeast plasmids, vectors derived from combinations of plasmids and phage DNA, and viral nucleic acid (RNA or DNA) vectors.
[0163] A recombinant expression vector can be designed for expression of a GIPR protein in prokaryotic (e.g., E. coli) or eukaryotic cells (e.g., insect cells, using baculovirus expression vectors, yeast cells, or mammalian cells). In one embodiment the host cell is a mammalian, non-human host cell. Representative host cells include those hosts typically used for cloning and expression, including Escherichia coli strains TOP1OF', TOP10, DH10B, DH5a, HB101, W3110, BL21(DE3) and BL21 (DE3)pLysS, BLUESCRIPT (Stratagene), mammalian cell lines CHO, CHO-K1, HEK293, 293-EBNA pIN vectors (Van Heeke & Schuster, J.
Biol.
Chem. 264: 5503-5509 (1989); pET vectors (Novagen, Madison Wis.).
Alternatively, the recombinant expression vector can be transcribed and translated in vitro, for example using T7 promoter regulatory sequences and T7 polymerase and an in vitro translation system.
Preferably, the vector contains a promoter upstream of the cloning site containing the nucleic acid sequence encoding the polypeptide. Examples of promoters, which can be switched on and off, include the lac promoter, the T7 promoter, the trc promoter, the tac promoter and the trp promoter.
[0164] Thus, provided herein are vectors comprising a nucleic acid sequence encoding GIPR
that facilitate the expression of recombinant GIPR. In various embodiments, the vectors comprise an operably linked nucleotide sequence which regulates the expression of GIPR. A
vector can comprise or be associated with any suitable promoter, enhancer, and other expression-facilitating elements. Examples of such elements include strong expression promoters (e.g., a human CMV IE promoter/enhancer, an RSV promoter, 5V40 promoter, 5L3-3 promoter, MMTV promoter, or HIV LTR promoter, EFlalpha promoter, CAG
promoter), effective poly (A) termination sequences, an origin of replication for plasmid product in E. coli, an antibiotic resistance gene as a selectable marker, and/or a convenient cloning site (e.g., a polylinker). Vectors also can comprise an inducible promoter as opposed to a constitutive promoter such as CMV IE. In one aspect, a nucleic acid comprising a sequence encoding a GIPR polypeptide which is operatively linked to a tissue specific promoter which promotes expression of the sequence in a metabolically-relevant tissue, such as liver or pancreatic tissue is provided.

[0165] In another aspect of the instant disclosure, host cells comprising the GIPR nucleic acids and vectors disclosed herein are provided. In various embodiments, the vector or nucleic acid is integrated into the host cell genome, which in other embodiments the vector or nucleic acid is extra-chromosomal.
[0166] Recombinant cells, such as yeast, bacterial (e.g., E. coli), and mammalian cells (e.g., immortalized mammalian cells) comprising such a nucleic acid, vector, or combinations of either or both thereof are provided. In various embodiments cells comprising a non-integrated nucleic acid, such as a plasmid, cosmid, phagemid, or linear expression element, which comprises a sequence coding for expression of a GIPR polypeptide, are provided.
[0167] A vector comprising a nucleic acid sequence encoding a GIPR polypeptide provided herein can be introduced into a host cell by transformation or by transfection. Methods of transforming a cell with an expression vector are well known.
[0168] A GIPR-encoding nucleic acid can be positioned in and/or delivered to a host cell or host animal via a viral vector. Any suitable viral vector can be used in this capacity. A viral vector can comprise any number of viral polynucleotides, alone or in combination with one or more viral proteins, which facilitate delivery, replication, and/or expression of the nucleic acid of the invention in a desired host cell. The viral vector can be a polynucleotide comprising all or part of a viral genome, a viral protein/nucleic acid conjugate, a virus-like particle (VLP), or an intact virus particle comprising viral nucleic acids and a GIPR
polypeptide-encoding nucleic acid. A viral particle viral vector can comprise a wild-type viral particle or a modified viral particle. The viral vector can be a vector which requires the presence of another vector or wild-type virus for replication and/or expression (e.g., a viral vector can be a helper-dependent virus), such as an adenoviral vector amplicon. Typically, such viral vectors consist of a wild-type viral particle, or a viral particle modified in its protein and/or nucleic acid content to increase transgene capacity or aid in transfection and/or expression of the nucleic acid (examples of such vectors include the herpes virus/AAV
amplicons). Typically, a viral vector is similar to and/or derived from a virus that normally infects humans. Suitable viral vector particles in this respect, include, for example, adenoviral vector particles (including any virus of or derived from a virus of the adenoviridae), adeno-associated viral vector particles (AAV vector particles) or other parvoviruses and parvoviral vector particles, papillomaviral vector particles, flaviviral vectors, alphaviral vectors, herpes viral vectors, pox virus vectors, retroviral vectors, including lentiviral vectors.
[0169] A GIPR polypeptide expressed as described herein can be isolated using standard protein purification methods. A GIPR polypeptide can be isolated from a cell in which is it naturally expressed or it can be isolated from a cell that has been engineered to express GIPR, for example a cell that does not naturally express GIPR.
[0170] Protein purification methods that can be employed to isolate a GIPR
polypeptide, as well as associated materials and reagents, are known in the art. Additional purification methods that may be useful for isolating a GIPR polypeptide can be found in references such as Bootcov MR, 1997, Proc. Natl. Acad. Sci. USA 94:11514-9, Fairlie WD, 2000, Gene 254:

67-76.
[0171] Antagonist antigen binding proteins that bind GIPR, including human GIPR (hGIPR) are provided herein. In one embodiment, the human GIPR has the sequence as such as set forth in SEQ ID NO: 1201. In another embodiment, the human GIPR has the sequence as such set forth in SEQ ID NO: 1203. In another embodiment, the human GIPR has the sequence as such set forth in SEQ ID NO: 1205.
[0172] The antigen binding proteins provided are polypeptides into which one or more complementary determining regions (CDRs), as described herein, are embedded and/or joined. In some antigen binding proteins, the CDRs are embedded into a "framework" region, which orients the CDR(s) such that the proper antigen binding properties of the CDR(s) are achieved. Certain antigen binding proteins described herein are antibodies or are derived from antibodies. In other antigen binding proteins, the CDR sequences are embedded in a different type of protein scaffold. The various structures are further described below.
[0173] The antigen binding proteins that are disclosed herein have a variety of utilities. The antigen binding proteins, for instance, are useful in specific binding assays, affinity purification of GIPR, and in screening assays to identify other antagonists of GIPR activity.
Other uses for the antigen binding proteins include, for example, diagnosis of GIPR-associated diseases or conditions and screening assays to determine the presence or absence of GIPR. Given that the antigen binding proteins that are provided are antagonists, the GIPR
antigen binding proteins have value in therapeutic methods in which it is useful to reduce weight gain, even while maintaining or increasing food intake, increasing %
fat mass and increasing % lean mass, improving glucose tolerance, decreasing insulin levels, decreasing cholesterol and triglyceride levels. Accordingly, the antigen binding proteins have utility in the treatment and prevention of diabetes, e.g., type 2 diabetes, obesity, dyslipidemia, elevated glucose levels or elevated insulin levels.
[0174] A variety of selective binding agents useful for modulating the activity of GIPR are provided. These agents include, for instance, antigen binding proteins that contain an antigen binding domain (e.g., scFvs, domain antibodies, and polypeptides with an antigen binding region) and specifically bind to a GIPR polypeptide, in particular human GIPR.
Some of the agents, for example, are useful in enhancing the activity of GIPR, and can activate one or more activities associated with GIPR.
[0175] In general the antigen binding proteins that are provided typically comprise one or more CDRs as described herein (e.g., 1, 2, 3, 4, 5 or 6). In some instances, the antigen binding protein comprises (a) a polypeptide structure and (b) one or more CDRs that are inserted into and/or joined to the polypeptide structure. The polypeptide structure can take a variety of different forms. For example, it can be, or comprise, the framework of a naturally occurring antibody, or fragment or variant thereof, or may be completely synthetic in nature.
Examples of various polypeptide structures are further described below.
[0176] In certain embodiments, the polypeptide structure of the antigen binding proteins is an antibody or is derived from an antibody. Accordingly, examples of certain antigen binding proteins that are provided include, but are not limited to, monoclonal antibodies, bispecific antibodies, minibodies, domain antibodies such as Nanobodies0, synthetic antibodies (sometimes referred to herein as "antibody mimetics"), chimeric antibodies, humanized antibodies, human antibodies, antibody fusions, and portions or fragments of each, respectively. In some instances, the antigen binding protein is an immunological fragment of a complete antibody (e.g., a Fab, a Fab', a F(ab')2). In other instances the antigen binding protein is a scFv that uses CDRs from an antibody of the present invention.
[0177] The antigen binding proteins as provided herein specifically bind to a human GIPR. In a specific embodiment, the antigen binding protein specifically binds to human GIPR
comprising or consisting of the amino acid sequence of SEQ ID NO: 1201. In a specific embodiment, the antigen binding protein specifically binds to human GIPR
comprising or consisting of the amino acid sequence of SEQ ID NO: 1203. In a specific embodiment, the antigen binding protein specifically binds to human GIPR comprising or consisting of the amino acid sequence of SEQ ID NO: 1205.
[0178] The antigen binding proteins that are provided are antagonists and typically have one, two, three, four, five, six, seven or all eight of the following characteristics:
[0179] (a) ability to prevent or reduce binding of GIP to GIPR, where the levels can be measured, for example, by the methods such as radioactive- or fluorescence-labeled ligand binding study, or by the methods described herein (e.g. cAMP assay or other functional assays). The decrease can be at least 10, 25, 50, 100% or more relative to the pre-treatment levels of SEQ ID NO: 1201, 1203 or 1205 under comparable conditions.
[0180] (b) ability to decrease blood glucose;

[0181] (c) ability to increase glucose tolerance;
[0182] (d) ability to increase insulin sensitivity;
[0183] (e) ability to decrease body weight or reduce body weight gain;
[0184] (f) ability to decrease fat mass or decrease inflammation in fat tissue;
[0185] (g) ability to decrease fasting insulin levels;
[0186] (h) ability to decrease circulating cholesterol levels;
[0187] (i) ability to decrease circulating triglyceride levels;
[0188] (j) ability to decrease liver steatosis or reduce triglyceride level in liver;
[0189] (k) ability to decrease AST, ALT, and/or ALP levels.
[0190] In one embodiment, a GIPR antigen binding protein has one or more of the following activities:
[0191] (a) binds human GIPR such that KD is <200 nM, is <150 nM, is <100 nM
, is <50 nM, is <10 nM, is <5 nM, is <2 nM, or is <1 nM, e.g., as measured via a surface plasma resonance or kinetic exclusion assay technique.
[0192] (b) has a half-life in human serum of at least 3 days;
[0193] Some antigen binding proteins that are provided have an on-rate (ka) for GIPR of at least 104/ M x seconds, at least 105/M x seconds, or at least 106/M x seconds as measured, for instance, as described below. Certain antigen binding proteins that are provided have a slow dissociation rate or off-rate. Some antigen binding proteins, for instance, have a kd (off-rate) of lx 10-2 s-1 , or lx 10-3 s-1, or lx 10-4 s-1 , or lx 10-5 s-1 . In certain embodiments, the antigen binding protein has a KD (equilibrium binding affinity) of less than 25 pM, 50 pM, 100 pM, 500 pM, 1 nM, 5 nM, 10 nM, 25 nM or 50 nM.
[0194] Depending on the assay, the binding of an antigen binding protein to its target can also be measured as an EC50 (the concentration of antigen binding protein that gives a half-maximal response when bound to target). An EC50 for an anti-GIPR antigen binding protein of the present invention can be determined by incubating different concentrations of antigen binding protein with cells expressing GIPR. Anti-GIPR antigen binding proteins of the present invention can have EC5Os less 200 nM, 150nM, 125 nM, 100 nM, 90 nM, 80 nM, 70 nM, 60 nM, 50 nM, 40 nM, or 30 nM.
[0195] An IC50 (the half maximal inhibitory concentration: a measure of the effectiveness of an antigen binding protein in inhibiting a specific biological or biochemical function) can also be used to measure the activity of anti-GIPR antigen binding protein. An IC 50 can be measured using a functional assay. For example, such an assay can be used for the quantitative determination of cAMP in HEK 293T cells expressing the human GIPR
or cynomolgus monkey GIPR. GIP binding causes GIPR conformation change, stimulating the G protein to active adenylate cyclase resulting in cAMP production from ATP.
Antibody binding to GIPR prevents GIP binding to GIPR with the result being less cAMP.
This is measurable by a cAMP assay. Anti-GIPR antigen binding proteins of the present invention can have IC50s less 200 nM, 150nM, 125 nM, 100 nM, 90 nM, 80 nM, 70 nM, 60 nM, nM, 40 nM, 30 nM, 29 nM, 28 nM, 27 nM, 26 nM, 25 nM, 24 nM, 23 nM, 22 nM, 21 mM, 20 nM, 19 nM, 18 nM, 17 nM, 16 nM, 15 nM, 14 nM, 13 nM, 12 nM, 11 mM, 10 nM, 9 nM, 8 nM, 7 nM, 6 nM, 5 nM, 4 nM, 3 nM, 2 nM, or 1 nM.
[0196] In another aspect, an antigen-binding protein is provided having a half-life of at least one day in vitro or in vivo (e.g., when administered to a human subject). In one embodiment, the antigen binding protein has a half-life of at least three days. In various other embodiments, the antigen binding protein has a half-life of 4, 5, 6, 7, 8,9, 10, 15, 20, 25, 30, 40, 50, or 60 days or longer. In another embodiment, the antigen binding protein is derivatized or modified such that it has a longer half-life as compared to the underivatized or unmodified antibody. In another embodiment, the antigen binding protein contains point mutations to increase serum half-life. Further details regarding such mutant and derivatized forms are provided below.
[0197] Some of the antigen binding proteins that are provided have the structure typically associated with naturally occurring antibodies. The structural units of these antibodies typically comprise one or more tetramers, each composed of two identical couplets of polypeptide chains, though some species of mammals also produce antibodies having only a single heavy chain. In a typical antibody, each pair or couplet includes one full-length "light"
chain (in certain embodiments, about 25 kDa) and one full-length "heavy" chain (in certain embodiments, about 50-70 kDa). Each individual immunoglobulin chain is composed of several "immunoglobulin domains", each consisting of roughly 90 to 110 amino acids and expressing a characteristic folding pattern. These domains are the basic units of which antibody polypeptides are composed. The amino-terminal portion of each chain typically includes a variable domain that is responsible for antigen recognition. The carboxy-terminal portion is more conserved evolutionarily than the other end of the chain and is referred to as the "constant region" or "C region". Human light chains generally are classified as kappa and lambda light chains, and each of these contains one variable domain and one constant domain. Heavy chains are typically classified as mu, delta, gamma, alpha, or epsilon chains, and these define the antibody's isotype as IgM, IgD, IgG, IgA, and IgE, respectively. IgG has several subtypes, including, but not limited to, IgGl, IgG2, IgG3, and IgG4.
IgM subtypes include IgM, and IgM2. IgA subtypes include IgAl and IgA2. In humans, the IgA
and IgD
isotypes contain four heavy chains and four light chains; the IgG and IgE
isotypes contain two heavy chains and two light chains; and the IgM isotype contains five heavy chains and five light chains. The heavy chain C region typically comprises one or more domains that may be responsible for effector function. The number of heavy chain constant region domains will depend on the isotype. IgG heavy chains, for example, each contain three C region domains known as CHL CH2 and CH3. The antibodies that are provided can have any of these isotypes and subtypes. In certain embodiments, the GIPR antibody is of the IgGl, IgG2, or IgG4 subtype. The terms "GIPR antibody" and "anti-GIPR antibody" are used interchangeably throughout this application and figures. Both terms refer to an antibody that binds to GIPR.
[0198] In full-length light and heavy chains, the variable and constant regions are joined by a "J" region of about twelve or more amino acids, with the heavy chain also including a "D"
region of about ten more amino acids. See, e.g. Fundamental Immunology, 2nd ed., Ch. 7 (Paul, W., ed.) 1989, New York: Raven Press (hereby incorporated by reference in its entirety for all purposes). The variable regions of each light/heavy chain pair typically form the antigen binding site.
[0199] For the antibodies provided herein, the variable regions of immunoglobulin chains generally exhibit the same overall structure, comprising relatively conserved framework regions (FR) joined by three hypervariable regions, more often called "complementarity determining regions" or CDRs. The CDRs from the two chains of each heavy chain/light chain pair mentioned above typically are aligned by the framework regions to form a structure that binds specifically with a specific epitope on GIPR. From N-terminal to C-terminal, naturally-occurring light and heavy chain variable regions both typically conform with the following order of these elements: FR1, CDR1, FR2, CDR2, FR3, CDR3 and FR4.
A numbering system has been devised for assigning numbers to amino acids that occupy positions in each of these domains. This numbering system is defined in Kabat Sequences of Proteins of Immunological Interest (1987 and 1991, NIH, Bethesda, Md.), or Chothia &
Lesk, 1987, J. Mol. Biol. 196:901-917; Chothia et al., 1989, Nature 342:878-883.
[0200] The sequence information for specific antibodies prepared and identified as described in the Examples below is summarized in TABLE 1. Thus, in an embodiment, an antigen binding protein is an antibody with the CDR, variable domain and light and heavy chain sequences as specified in one of the rows of TABLE 1.

[0201] SEQ ID NOs have been assigned to variable light chain, variable heavy chain, light chain, heavy chain, CDRL1, CDRL2, CDRL3, CDRH1, CDRH2, and CDRH3 sequences of the antibodies and fragments thereof of the present invention and are shown in TABLE 1.
SEQ ID NOs have also been assigned to polynucleotides encoding the variable light chain, variable heavy chain, light chain, heavy chain, CDRL1, CDRL2, CDRL3, CDRH1, CDRH2, and CDRH3 sequences of the antibodies and fragments thereof of the present invention and are shown in TABLE 2. The antigen binding proteins of the present invention can be identified by SEQ ID NO, but also by construct name (e.g., 2C2.005) or identifier number (e.g., iPS:336175). The antigen binding proteins identified in Tables 1-5 below can be grouped into families based on construct name. For example, the "4B1 family"
includes the constructs 4B1, 4B1.010, 4B1.011, 4B1.012, 4B1.013, 4B1.014, 4B1.015, and 4B1.016.
[0202] The various light chain and heavy chain variable regions provided herein are depicted in TABLE 3. Each of these variable regions may be attached to a heavy or light chain constant regions to form a complete antibody heavy and light chain, respectively.
Furthermore, each of the so generated heavy and light chain sequences may be combined to form a complete antibody structure.

Table 1. Amino acid SEQ ID NOs.
Construct VL VII LC HC CDRL1 CDRL2 CDRL3 CDRH1 CDRH2 CDRH3 n.) 2G10.303 723 724 963 964 4 5 6 364 365 366 =
2G10.304 727 728 967 968 10 11 12 370 371 372 0 e 2G10.323 731 732 971 972 16 17 18 376 377 378 c +4 2G10.309 735 736 975 976 22 23 24 382 383 384 =
o 2G10.316 739 740 979 980 28 29 30 388 389 2G10.604 743 744 983 984 34 35 36 394 395 2G10.609 747 748 987 988 40 41 42 400 401 2G10.603 751 752 991 992 46 47 48 406 407 2G10.318 755 756 995 996 52 53 54 412 413 2G10.324 759 760 999 1000 58 59 60 418 419 2G10.322 763 764 1003 1004 64 65 66 424 425 2G10.315 767 768 1007 1008 70 71 72 430 431 2G10.331 771 772 1011 1012 76 77 78 436 437 2G10.320 775 776 1015 1016 82 83 84 442 443 2G10.328 779 780 1019 1020 88 89 90 448 449 2G10.333 783 784 1023 1024 94 95 96 454 455 2G10.301 787 788 1027 1028 100 101 102 460 461 462 .
2G10.601 791 792 1031 1032 106 107 108 466 467 2G10.326 795 796 1035 1036 112 113 114 472 473 2G10.308 799 800 1039 1040 118 119 120 478 479 2G10.608 803 804 1043 1044 124 125 126 484 485 2G10.336 807 808 1047 1048 130 131 132 490 491 2G10.344 811 812 1051 1052 136 137 138 496 497 2G10.310 815 816 1055 1056 142 143 144 502 503 2G10.610 819 820 1059 1060 148 149 150 508 509 2G10.312 823 824 1063 1064 154 155 156 514 515 2G10.329 827 828 1067 1068 160 161 162 520 521 2G10.327 831 832 1071 1072 166 167 168 526 527 2G10.338 835 836 1075 1076 172 173 174 532 533 534 n 2G10.314 839 840 1079 1080 178 179 180 538 539 2G10.337 843 844 1083 1084 184 185 186 544 545 n.) 2G10.341 847 848 1087 1088 190 191 192 550 551 552 o 2G10.302 851 852 1091 1092 196 197 198 556 557 558 oe -a-, 2G10.602 855 856 1095 1096 202 203 204 562 563 oe 2G10.325 859 860 1099 1100 208 209 210 568 569 570 o oe 2G10.343 863 864 1103 1104 214 215 216 574 575 2G10.313 867 868 1107 1108 220 221 222 580 581 2G10.317 871 872 1111 1112 226 227 228 586 587 2G10.311 875 876 1115 1116 232 233 234 592 593 594 -- n.) o 2G10.306 879 880 1119 1120 238 239 240 598 599 oe 2G10.606 883 884 1123 1124 244 245 246 604 605 606 -- t:1 2G10.347 887 888 1127 1128 250 251 252 610 611 612 --.1 o 2G10.348 891 892 1131 1132 256 257 258 616 617 --.1 2G10.346 895 896 1135 1136 262 263 264 622 623 2G10.647 899 900 1139 1140 268 269 270 628 629 2G10.649 903 904 1143 1144 274 275 276 634 635 2G10.305 907 908 1147 1148 280 281 282 640 641 2G10.605 911 912 1151 1152 286 287 288 646 647 2G10.340 915 916 1155 1156 292 293 294 652 653 2G10.334 919 920 1159 1160 298 299 300 658 659 2G10.339 923 924 1163 1164 304 305 306 664 665 2G10.307 927 928 1167 1168 310 311 312 670 671 2G10.607 931 932 1171 1172 316 317 318 676 677 ,..
2G10.321 935 936 1175 1176 322 323 324 682 683 684 .
N, , 2G10.342 939 940 1179 1180 328 329 330 688 689 690 -- .
2G10.319 943 944 1183 1184 334 335 336 694 695 696 -- ^, 2G10.332 947 948 1187 1188 340 341 342 700 701 702 -- , , 2G10.345 951 952 1191 1192 346 347 348 706 707 708 -- , , 2G10.335 955 956 1195 1196 352 353 354 712 713 714 -- ,..
, 2G10.330 959 960 1199 1200 358 359 360 718 719 iPS:529381 1286 1287 1288 1289 1290 1291 1292 1293 1294 1295 iPS:529382 1296 1297 1298 1299 1300 1301 1302 1303 1304 1305 iPS:529397 1306 1307 1308 1309 1310 1311 1312 1313 iPS:529399 1316 1317 1318 1319 1320 1321 1322 1323 iPS:529400 1326 1327 1328 1329 1330 1331 1332 1333 iPS:529403 1336 1337 1338 1339 1340 1341 1342 1343 n iPS:529404 1346 1347 1348 1349 1350 1351 1352 1353 iPS:529405 1356 1357 1358 1359 1360 1351 1352 1353 cp n.) o 1-, oe oe cA
oe Table 2. Nucleic acid SEQ ID NOs.
Construct VL VII LC HC CDRL1 CDRL2 CDRL3 CDRH1 CDRH2 CDRH3 n.) 2G10.303 721 722 961 962 1 2 3 361 362 363 =
2G10.304 725 726 965 966 7 8 9 367 368 369 ce 0 2G10.323 729 730 969 970 13 14 15 373 374 2G10.309 733 734 973 974 19 20 21 379 380 381 =
o 2G10.316 737 738 977 978 25 26 27 385 386 2G10.604 741 742 981 982 31 32 33 391 392 2G10.609 745 746 985 986 37 38 39 397 398 2G10.603 749 750 989 990 43 44 45 403 404 2G10.318 753 754 993 994 49 50 51 409 410 2G10.324 757 758 997 998 55 56 57 415 416 2G10.322 761 762 1001 1002 61 62 63 421 422 2G10.315 765 766 1005 1006 67 68 69 427 428 2G10.331 769 770 1009 1010 73 74 75 433 434 2G10.320 773 774 1013 1014 79 80 81 439 440 2G10.328 777 778 1017 1018 85 86 87 445 446 2G10.333 781 782 1021 1022 91 92 93 451 452 2G10.301 785 786 1025 1026 97 98 99 457 458 459 .
2G10.601 789 790 1029 1030 103 104 105 463 464 2G10.326 793 794 1033 1034 109 110 111 469 470 2G10.308 797 798 1037 1038 115 116 117 475 476 2G10.608 801 802 1041 1042 121 122 123 481 482 2G10.336 805 806 1045 1046 127 128 129 487 488 2G10.344 809 810 1049 1050 133 134 135 493 494 2G10.310 813 814 1053 1054 139 140 141 499 500 2G10.610 817 818 1057 1058 145 146 147 505 506 2G10.312 821 822 1061 1062 151 152 153 511 512 2G10.329 825 826 1065 1066 157 158 159 517 518 2G10.327 829 830 1069 1070 163 164 165 523 524 2G10.338 833 834 1073 1074 169 170 171 529 530 531 n 2G10.314 837 838 1077 1078 175 176 177 535 536 2G10.337 841 842 1081 1082 181 182 183 541 542 543 ci ) n.) 2G10.341 845 846 1085 1086 187 188 189 547 548 549 o 2G10.302 849 850 1089 1090 193 194 195 553 554 555 cee -a-, 2G10.602 853 854 1093 1094 199 200 201 559 560 cio 2G10.325 857 858 1097 1098 205 206 207 565 566 567 o o o 2G10.343 861 862 1101 1102 211 212 213 571 572 2G10.313 865 866 1105 1106 217 218 219 577 578 2G10.317 869 870 1109 1110 223 224 225 583 584 2G10.311 873 874 1113 1114 229 230 231 589 590 591 n.) o 2G10.306 877 878 1117 1118 235 236 237 595 596 oe 2G10.606 881 882 1121 1122 241 242 243 601 602 603 t:1 2G10.347 885 886 1125 1126 247 248 249 607 608 609 --.1 o 2G10.348 889 890 1129 1130 253 254 255 613 614 --.1 2G10.346 893 894 1133 1134 259 260 261 619 620 2G10.647 897 898 1137 1138 265 266 267 625 626 2G10.649 901 902 1141 1142 271 272 273 631 632 2G10.305 905 906 1145 1146 277 278 279 637 638 2G10.605 909 910 1149 1150 283 284 285 643 644 2G10.340 913 914 1153 1154 289 290 291 649 650 2G10.334 917 918 1157 1158 295 296 297 655 656 2G10.339 921 922 1161 1162 301 302 303 661 662 2G10.307 925 926 1165 1166 307 308 309 667 668 2G10.607 929 930 1169 1170 313 314 315 673 674 ,..
2G10.321 933 934 1173 1174 319 320 321 679 680 r., 2G10.342 937 938 1177 1178 325 326 327 685 686 687 , 2G10.319 941 942 1181 1182 331 332 333 691 692 2G10.332 945 946 1185 1186 337 338 339 697 698 699 , , 2G10.345 949 950 1189 1190 343 344 345 703 704 705 , , 2G10.335 953 954 1193 1194 349 350 351 709 710 711 ,..
, 2G10.330 957 958 1197 1198 355 356 357 715 716 iPS:529381 1377 1378 1361 1362 iPS:529382 1379 1380 1363 1364 iPS:529397 1381 1382 1365 1366 iPS:529399 1383 1384 1367 1368 iPS:529400 1385 1386 1369 1370 iPS:529403 1387 1388 1371 1372 IV
n iPS:529404 1389 1390 1373 iPS:529405 1391 1392 1375 1376 cp n.) o 1-, oe CO-c,.) oe o c,.) oe Table 3. Exemplary Variable Light and Variable Heavy Regions: Nucleic Acid ("NA") and Amino Acid ("AA") Sequences k:AwTypeggaggagnmaggkeNNitokititimagnmaggnmaaaognagammognitWANtogiottomonamognm na cao GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGT
GTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGG CCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGC
GCCAGTCAGAGTGTTGATAGACACTTAGCCTGGTAC ATCTGGATTCACCTTCAGTAACTATGGCATGCACTG
CAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATC GGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTGGG
TACGAAGCAGCCACCAGGGCCACTGGTATCCCAGC TGGCAGCTATATGGTTTGATGCAAGTGATAAATACT
CAGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCAC ATGCAGACGCCGTGAAGGGCCGATTCACCATCTCCA
NA TCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGC GAGACAACTCCAAGAACACGCTGTATCTGCAAATG
AGTTTATTACTGTCAGCAGTATCAGAACTGGCCTCT AACAGCCTGAGAGCCGAGGACACGGCTGTGTATTA
CACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA CTGTGCGAGAGATTTGGCGATTTTTGGAGTGGTCCC
CGACTACTGGGGCCAGGGAACCCTGGTCACCGTGTC
TAGT
(SEQ ID NO: 721) (SEQ ID NO: 722) EIVMTQ SP ATL SV SP GERATL SCRASQ SVDRHLAWYQ QVQLVE SGGGVVQPGRSLRL
SCAASGFTFSNYGMHW
QKP GQAPRLLIYEAATRATGIP ARF S GS GS GTEFTL TI S VRQAP GE GLEWVAAIWFD
ASDKYYADAVKGRFTI SR
n AA SLQSEDFAVYYCQQYQNWPLTFGGGTKVEIK
DNSKNTLYLQMNSLRAEDTAVYYCARDLAIFGVVPD
YWGQGTLVTVSS
(SEQ ID NO: 723) (SEQ ID NO: 724) GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGT
GTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGG CCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGC
GCCAGTCAGAGTGTTAACAGACACTTAGCCTGGTAC ATCTGGATTCACCTTCAGTAACTATGGCATGCACTG
CAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATC GGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTGGG
TACGAAGCAGCCACCAGGGCCACTGGTATCCCAGC TGGCAGCTATATGGTTTGATGCAAGTGATAAATACT
CAGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCAC ATGCAGACGCCGTGAAGGGCCGATTCACCATCTCCA
NA TCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGC GAGACAACTCCAAGAACACGCTGTATCTGCAAATG
AGTTTATTACTGTCAGCAGTATCAGAACTGGCCTCT AACAGCCTGAGAGCCGAGGACACGGCTGTGTATTA
CACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA CTGTGCGAGAGATTTGGCGATTTTTGGAGTGGTCCC

CGACTACTGGGGCCAGGGAACCCTGGTCACCGTGTC
TAGT
(SEQ ID NO: 725) (SEQ ID NO: 726) ceo oo oo EIVMTQ SP ATL SV SP GERATL SCRASQ SVNRHLAWYQ QVQLVE SGGGVVQPGRSLRL
SCAASGFTFSNYGMHW
QKP GQAPRLLIYEAATRATGIP ARF S GS GS GTEFTL TI S VRQAP GE GLEWVAAIWFD
ASDKYYADAVKGRFTI SR
AA SLQSEDFAVYYCQQYQNWPLTFGGGTKVEIK

YWGQGTLVTVSS
n.) o (SEQ ID NO: 727) (SEQ ID NO: 728) oe i-J
GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGT
c,.) --.1 GTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGG CCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGC
o --.1 GCCAGTCAGAGTGTTCATAGACACTTAGCCTGGTAC ATCTGGATTCACCTTCAGTAACTATGGCATGCACTG
CAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATC GGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTGGG
TACGAAGCAGCCACCAGGGCCACTGGTATCCCAGC TGGCAGCTATATGGTTTGATGCAAGTGATAAATACT
CAGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCAC ATGCAGACGCCGTGAAGGGCCGATTCACCATCTCCA
NA
TCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGC GAGACAACTCCAAGAACACGCTGTATCTGCAAATG
AGTTTATTACTGTCAGCAGTATCAGAACTGGCCTCT AACAGCCTGAGAGCCGAGGACACGGCTGTGTATTA
CACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA CTGTGCGAGAGATTTGGCGATTTTTGGAGTGGTCCC
CGACTACTGGGGCCAGGGAACCCTGGTCACCGTGTC
TAGT
p (SEQ ID NO: 729) (SEQ ID NO: 730) .
L.
EIVMTQ SP ATL SV SP GERATL SCRASQ SVHRHLAWYQ QVQLVE SGGGVVQPGRSLRL
SCAASGFTFSNYGMHW "
, re) QKP GQAPRLLIYEAATRATGIP ARF S GS GS GTEFTL TI S VRQAP GE GLEWVAAIWFD
ASDKYYADAVKGRFTI SR .
N, 'el o AA SLQSEDFAVYYCQQYQNWPLTFGGGTKVEIK
DNSKNTLYLQMNSLRAEDTAVYYCARDLAIFGVVPD
PI YWGQGTLVTVSS
(SEQ ID NO: 731) (SEQ ID NO: 732) , L.
, GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGT
GTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGG CCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGC
GCCAGTCAGAGTGTTGAAAGACACTTAGCCTGGTAC ATCTGGATTCACCTTCAGTAACTATGGCATGCACTG
CAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATC GGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTGGG
TACGAAGCAGCCACCAGGGCCACTGGTATCCCAGC TGGCAGCTATATGGTTTGATGCAAGTGATAAATACT
CAGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCAC ATGCAGACGCCGTGAAGGGCCGATTCACCATCTCCA
NA
TCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGC GAGACAACTCCAAGAACACGCTGTATCTGCAAATG
AGTTTATTACTGTCAGCAGTATCAGAACTGGCCTCT AACAGCCTGAGAGCCGAGGACACGGCTGTGTATTA

n c, CACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA

o fl CGACTACTGGGGCCAGGGAACCCTGGTCACCGTGTC
cp o n.) PI TAGT
(SEQ ID NO: 733) (SEQ ID NO: 734) o oe 'a oe cA
oe EIVMTQ SP ATL SV SPGERATL SCRASQ SVERHLAWYQ QVQLVE SGGGVVQPGRSLRL
SCAASGFTFSNYGMHW
QKP GQAPRLLIYEAATRATGIP ARF S GS GS GTEFTL TI S VRQAP GE GLEWVAAIWFD
ASDKYYADAVKGRFTI SR
AA SLQSEDFAVYYCQQYQNWPLTFGGGTKVEIK

YWGQGTLVTVSS
n.) o (SEQ ID NO: 735) (SEQ ID NO: 736) oe i-J
GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGT
c,.) --.1 GTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGG CCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGC
o --.1 GCCAGTCAGAGTGTTTTCAGACACTTAGCCTGGTAC ATCTGGATTCACCTTCAGTAACTATGGCATGCACTG
CAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATC GGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTGGG
TACGAAGCAGCCACCAGGGCCACTGGTATCCCAGC TGGCAGCTATATGGTTTGATGCAAGTGATAAATACT
CAGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCAC ATGCAGACGCCGTGAAGGGCCGATTCACCATCTCCA
NA
TCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGC GAGACAACTCCAAGAACACGCTGTATCTGCAAATG
AGTTTATTACTGTCAGCAGTATCAGAACTGGCCTCT AACAGCCTGAGAGCCGAGGACACGGCTGTGTATTA
CACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA CTGTGCGAGAGATTTGGCGATTTTTGGAGTGGTCCC
CGACTACTGGGGCCAGGGAACCCTGGTCACCGTGTC
TAGT
p (SEQ ID NO: 737) (SEQ ID NO: 738) .
L.
EIVMTQ SP ATL SVSP GERATL SCRASQ SVFRHLAWYQ QVQLVE SGGGVVQPGRSLRL
SCAASGFTFSNYGMHW "
, QKP GQAPRLLIYEAATRATGIP ARF S GS GS GTEFTL TI S VRQAP GE GLEWVAAIWFD
ASDKYYADAVKGRFTI SR .
N, '1 o AA SLQSEDFAVYYCQQYQNWPLTFGGGTKVEIK
DNSKNTLYLQMNSLRAEDTAVYYCARDLAIFGVVPD
PI YWGQGTLVTVSS
(SEQ ID NO: 739) (SEQ ID NO: 740) , L.
, GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGT
GTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGG CCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGC
GCCAGTCAGAGTGTTAACAGACACTTAGCCTGGTAC ATCTGGATTCACCTTCAGTAACTATGGCATGCACTG
CAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATC GGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTGGG
TACGAAGCAGCCACCAGGGCCACTGGTATCCCAGC TGGCAGCTATATGGTTTGATGCAAGTGATAAATACT
CAGGGTCAGTGGCAGTGGGTCTGGGACAGAGTTCA ATGCAGACGCCGTGAAGGGCCGATTCACCATCTCCA
NA
CTCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTG GAGACAACTCCAAGAACACGCTGTATCTGCAAATG
CAGTTTATTACTGTCAGCAGTATCAGAACTGGCCTC AACAGCCTGAGAGCCGAGGACACGGCTGTGTATTA

n .7r TCACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA

o `z.
CGACTACTGGGGCCAGGGAACCCTGGTCACCGTGTC
cp o n.) PI TAGT
(SEQ ID NO: 741) (SEQ ID NO: 742) o oe 'a oe cA
oe EIVMTQ SP ATL SV SP GERATL SCRASQ SVNRHLAWYQ QVQLVE SGGGVVQPGRSLRL
SCAASGFTFSNYGMHW
QKP GQAPRLLIYEAATRATGIP ARVS GS GS GTEFTL TI S VRQAP GE GLEWVAAIWFD
ASDKYYADAVKGRFTI SR
AA SLQSEDFAVYYCQQYQNWPLTFGGGTKVEIK

YWGQGTLVTVSS
n.) o (SEQ ID NO: 743) (SEQ ID NO: 744) oe i-J
GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGT
c,.) --.1 GTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGG CCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGC
o --.1 GCCAGTCAGAGTGTTGAAAGACACTTAGCCTGGTAC ATCTGGATTCACCTTCAGTAACTATGGCATGCACTG
CAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATC GGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTGGG
TACGAAGCAGCCACCAGGGCCACTGGTATCCCAGC TGGCAGCTATATGGTTTGATGCAAGTGATAAATACT
CAGGGTCAGTGGCAGTGGGTCTGGGACAGAGTTCA ATGCAGACGCCGTGAAGGGCCGATTCACCATCTCCA
NA
CTCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTG GAGACAACTCCAAGAACACGCTGTATCTGCAAATG
CAGTTTATTACTGTCAGCAGTATCAGAACTGGCCTC AACAGCCTGAGAGCCGAGGACACGGCTGTGTATTA
TCACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA CTGTGCGAGAGATTTGGCGATTTTTGGAGTGGTCCC
CGACTACTGGGGCCAGGGAACCCTGGTCACCGTGTC
TAGT
p (SEQ ID NO: 745) (SEQ ID NO: 746) .
L.
EIVMTQ SP ATL SV SPGERATL SCRASQ SVERHLAWYQ QVQLVE SGGGVVQPGRSLRL
SCAASGFTFSNYGMHW "
, o, QKP GQAPRLLIYEAATRATGIP ARVS GS GS GTEFTL TI S VRQAP GE GLEWVAAIWFD
ASDKYYADAVKGRFTI SR .
o N, AA SLQSEDFAVYYCQQYQNWPLTFGGGTKVEIK
DNSKNTLYLQMNSLRAEDTAVYYCARDLAIFGVVPD
PI YWGQGTLVTVSS
(SEQ ID NO: 747) (SEQ ID NO: 748) , L.
, GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGT
GTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGG CCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGC
GCCAGTCAGAGTGTTGATAGACACTTAGCCTGGTAC ATCTGGATTCACCTTCAGTAACTATGGCATGCACTG
CAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATC GGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTGGG
TACGAAGCAGCCACCAGGGCCACTGGTATCCCAGC TGGCAGCTATATGGTTTGATGCAAGTGATAAATACT
CAGGGTCAGTGGCAGTGGGTCTGGGACAGAGTTCA ATGCAGACGCCGTGAAGGGCCGATTCACCATCTCCA
NA
CTCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTG GAGACAACTCCAAGAACACGCTGTATCTGCAAATG
CAGTTTATTACTGTCAGCAGTATCAGAACTGGCCTC AACAGCCTGAGAGCCGAGGACACGGCTGTGTATTA

n re) TCACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA

o `z.
CGACTACTGGGGCCAGGGAACCCTGGTCACCGTGTC
cp o n.) PI TAGT
(SEQ ID NO: 749) (SEQ ID NO: 750) o oe 'a oe cA
oe EIVMTQ SP ATL SV SP GERATL SCRASQ SVDRHLAWYQ QVQLVE SGGGVVQPGRSLRL
SCAASGFTFSNYGMHW
QKP GQAPRLLIYEAATRATGIP ARVS GS GS GTEFTL TI S VRQAP GE GLEWVAAIWFD
ASDKYYADAVKGRFTI SR
AA SLQSEDFAVYYCQQYQNWPLTFGGGTKVEIK

YWGQGTLVTVSS
n.) o (SEQ ID NO: 751) (SEQ ID NO: 752) oe i-J
GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGT
c,.) --.1 GTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGG CCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGC
o --.1 GCCAGTCAGAGTGTTCTGAGTCACTTAGCCTGGTAC ATCTGGATTCACCTTCAGTAACTATGGCATGCACTG
CAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATC GGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTGGG
TACGAAGCAGCCACCAGGGCCACTGGTATCCCAGC TGGCAGCTATATGGTTTGATGCAAGTGATAAATACT
CAGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCAC ATGCAGACGCCGTGAAGGGCCGATTCACCATCTCCA
NA
TCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGC GAGACAACTCCAAGAACACGCTGTATCTGCAAATG
AGTTTATTACTGTCAGCAGTATAACAACTGGCCTCT AACAGCCTGAGAGCCGAGGACACGGCTGTGTATTA
CACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA CTGTGCGAGAGATTTGGCGATTTTTGGAGTGGTCCC
CGACTACTGGGGCCAGGGAACCCTGGTCACCGTGTC
TAGT
p (SEQ ID NO: 753) (SEQ ID NO: 754) .
L.
EIVMTQ SP ATL SV SP GERATL SCRASQ SVL SHL AWYQ QVQLVE SGGGVVQPGRSLRL
SCAASGFTFSNYGMHW "
, co QKP GQAPRLLIYEAATRATGIP ARF S GS GS GTEFTL TI S VRQAP GE GLEWVAAIWFD
ASDKYYADAVKGRFTI SR .
N, n o AA SLQSEDFAVYYCQQYNNWPLTFGGGTKVEIK
DNSKNTLYLQMNSLRAEDTAVYYCARDLAIFGVVPD
PI YWGQGTLVTVSS
(SEQ ID NO: 755) (SEQ ID NO: 756) , L.
, GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGT
GTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGG CCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGC
GCCAGTCAGAGTGTTCTGAGTCACTTAGCCTGGTAC ATCTGGATTCACCTTCAGTAACTATGGCATGCACTG
CAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATC GGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTGGG
TACGAAGCAGCCACCAGGGCCACTGGTATCCCAGC TGGCAGCTATATGGTTTGATGCAAGTGATAAATACT
CAGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCAC ATGCAGACGCCGTGAAGGGCCGATTCACCATCTCCA
NA
TCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGC GAGACAACTCCAAGAACACGCTGTATCTGCAAATG
AGTTTATTACTGTCAGCAGTATCAGAACTGGCCTCT AACAGCCTGAGAGCCGAGGACACGGCTGTGTATTA

n .7r CACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA

n CGACTACTGGGGCCAGGGAACCCTGGTCACCGTGTC
cp o n.) PI TAGT
(SEQ ID NO: 757) (SEQ ID NO: 758) o oe 'a oe cA
oe EIVMTQ SP ATL SV SP GERATL SCRASQ SVL SHL AWYQ QVQLVE SGGGVVQPGRSLRL
SCAASGFTFSNYGMHW
QKP GQAPRLLIYEAATRATGIP ARF S GS GS GTEFTL TI S VRQAP GE GLEWVAAIWFD
ASDKYYADAVKGRFTI SR
AA SLQSEDFAVYYCQQYQNWPLTFGGGTKVEIK

YWGQGTLVTVSS
n.) o (SEQ ID NO: 759) (SEQ ID NO: 760) oe i-J
GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGT
c,.) --.1 GTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGG CCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGC
o --.1 GCCAGTCAGAGTGTTATGAGTCACTTAGCCTGGTAC ATCTGGATTCACCTTCAGTAACTATGGCATGCACTG
CAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATC GGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTGGG
TACGAAGCAGCCACCAGGGCCACTGGTATCCCAGC TGGCAGCTATATGGTTTGATGCAAGTGATAAATACT
CAGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCAC ATGCAGACGCCGTGAAGGGCCGATTCACCATCTCCA
NA
TCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGC GAGACAACTCCAAGAACACGCTGTATCTGCAAATG
AGTTTATTACTGTCAGCAGTATCAGAACTGGCCTCT AACAGCCTGAGAGCCGAGGACACGGCTGTGTATTA
CACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA CTGTGCGAGAGATTTGGCGATTTTTGGAGTGGTCCC
CGACTACTGGGGCCAGGGAACCCTGGTCACCGTGTC
TAGT
p (SEQ ID NO: 761) (SEQ ID NO: 762) .
L.
EIVMTQ SP ATL SV SP GERATL SCRASQ SVM SHL AWYQ QVQLVE SGGGVVQPGRSLRL
SCAASGFTFSNYGMHW "
, QKP GQAPRLLIYEAATRATGIP ARF S GS GS GTEFTL TI S VRQAP GE GLEWVAAIWFD
ASDKYYADAVKGRFTI SR .
N, n o AA SLQSEDFAVYYCQQYQNWPLTFGGGTKVEIK
DNSKNTLYLQMNSLRAEDTAVYYCARDLAIFGVVPD
PI YWGQGTLVTVSS
(SEQ ID NO: 763) (SEQ ID NO: 764) , L.
, GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGT
GTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGG CCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGC
GCCAGTCAGAGTGTTCTGACGCACTTAGCCTGGTAC ATCTGGATTCACCTTCAGTAACTATGGCATGCACTG
CAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATC GGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTGGG
TACGAAGCAGCCACCAGGGCCACTGGTATCCCAGC TGGCAGCTATATGGTTTGATGCAAGTGATAAATACT
CAGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCAC ATGCAGACGCCGTGAAGGGCCGATTCACCATCTCCA
NA
TCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGC GAGACAACTCCAAGAACACGCTGTATCTGCAAATG
AGTTTATTACTGTCAGCAGTATCAGAACTGGCCTCT AACAGCCTGAGAGCCGAGGACACGGCTGTGTATTA

n in CACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA

,-n CGACTACTGGGGCCAGGGAACCCTGGTCACCGTGTC
cp o n.) PI TAGT
(SEQ ID NO: 765) (SEQ ID NO: 766) o oe 'a oe cA
oe EIVMTQ SP ATL SV SP GERATL SCRASQ SVLTHLAWYQ QVQLVE SGGGVVQPGRSLRL
SCAASGFTFSNYGMHW
QKP GQAPRLLIYEAATRATGIP ARF S GS GS GTEFTL TI S VRQAP GE GLEWVAAIWFD
ASDKYYADAVKGRFTI SR
AA SLQSEDFAVYYCQQYQNWPLTFGGGTKVEIK

YWGQGTLVTVSS
n.) o (SEQ ID NO: 767) (SEQ ID NO: 768) oe i-J
GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGT
c,.) --.1 GTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGG CCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGC
o --.1 GCCAGTCAGAGTGTTGATCTGCACTTAGCCTGGTAC ATCTGGATTCACCTTCAGTAACTATGGCATGCACTG
CAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATC GGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTGGG
TACGAAGCAGCCACCAGGGCCACTGGTATCCCAGC TGGCAGCTATATGGTTTGATGCAAGTGATAAATACT
CAGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCAC ATGCAGACGCCGTGAAGGGCCGATTCACCATCTCCA
NA
TCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGC GAGACAACTCCAAGAACACGCTGTATCTGCAAATG
AGTTTATTACTGTCAGCAGTATCAGAACTGGCCTCT AACAGCCTGAGAGCCGAGGACACGGCTGTGTATTA
CACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA CTGTGCGAGAGATTTGGCGATTTTTGGAGTGGTCCC
CGACTACTGGGGCCAGGGAACCCTGGTCACCGTGTC
TAGT
p (SEQ ID NO: 769) (SEQ ID NO: 770) .
L.
EIVMTQ SP ATL SVSPGERATL SCRASQSVDLHLAWYQ QVQLVE SGGGVVQPGRSLRL
SCAASGFTFSNYGMHW "
, ,- QKP GQAPRLLIYEAATRATGIP ARF S GS GS GTEFTL TI S VRQAP GE GLEWVAAIWFD
ASDKYYADAVKGRFTI SR .
f el o AA SLQSEDFAVYYCQQYQNWPLTFGGGTKVEIK
DNSKNTLYLQMNSLRAEDTAVYYCARDLAIFGVVPD
PI YWGQGTLVTVSS
(SEQ ID NO: 771) (SEQ ID NO: 772) , L.
, GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGT
GTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGG CCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGC
GCCAGTCAGAGTGTTAGCGAACACTTAGCCTGGTAC ATCTGGATTCACCTTCAGTAACTATGGCATGCACTG
CAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATC GGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTGGG
TACGAAGCAGCCACCAGGGCCACTGGTATCCCAGC TGGCAGCTATATGGTTTGATGCAAGTGATAAATACT
CAGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCAC ATGCAGACGCCGTGAAGGGCCGATTCACCATCTCCA
NA
TCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGC GAGACAACTCCAAGAACACGCTGTATCTGCAAATG
AGTTTATTACTGTCAGCAGTATCAGAACTGGCCTCT AACAGCCTGAGAGCCGAGGACACGGCTGTGTATTA

n o CACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA

fl CGACTACTGGGGCCAGGGAACCCTGGTCACCGTGTC
cp o n.) PI TAGT
(SEQ ID NO: 773) (SEQ ID NO: 774) o oe 'a oe cA
oe EIVMTQ SP ATL SV SP GERATL SCRASQ SVSEHL AWYQ QVQLVE SGGGVVQPGRSLRL
SCAASGFTFSNYGMHW
QKP GQAPRLLIYEAATRATGIP ARF S GS GS GTEFTL TI S VRQAP GE GLEWVAAIWFD
ASDKYYADAVKGRFTI SR
AA SLQSEDFAVYYCQQYQNWPLTFGGGTKVEIK

WGQGTLVTVSS
n.) o (SEQ ID NO: 775) (SEQ ID NO: 776) oe i-J
GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGT
c,.) --.1 GTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGG CCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGC
o --.1 GCCAGTCAGAGTGTTAGCGAACACTTAGCCTGGTAC ATCTGGATTCACCTTCAGTAACTATGGCATGCACTG
CAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATC GGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTGGG
TACGAAGCAGCCACCAGGGCCACTGGTATCCCAGC TGGCAGCTATATGGTTTGATGCAAGTGATAAATACT
CAGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCAC ATGCAGACGCCGTGAAGGGCCGATTCACCATCTCCA
NA
TCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGC GAGACAACTCCAAGAACACGCTGTATCTGCAAATG
AGTTTATTACTGTCAGCAGTATCAGAACTGGCCTCT AACAGCCTGAGAGCCGAGGACACGGCTGTGTATTA
CACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA CTGTGCGAGAGATTTGGCGATTTTTGGAGTGGTCCC
CGACTACTGGGGCCAGGGAACCCTGGTCACCGTGTC
TAGT
p (SEQ ID NO: 777) (SEQ ID NO: 778) .
L.
EIVMTQ SP ATL SV SP GERATL SCRASQ SVSEHL AWYQ QVQLVE SGGGVVQPGRSLRL
SCAASGFTFSNYGMHW "
, co QKP GQAPRLLIYEAATRATGIP ARF S GS GS GTEFTL TI S VRQAP GE GLEWVAAIWFD
ASDKYYADAVKGRFTI SR .
N, n o AA SLQSEDFAVYYCQQYQNWPLTFGGGTKVEIK
DNSKNTLYLQMNSLRAEDTAVYYCARDLAIFGVVPD
PI YWGQGTLVTVSS
(SEQ ID NO: 779) (SEQ ID NO: 780) , L.
, GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGT
GTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGG CCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGC
GCCAGTCAGAGTGTTAGCCGGCACTTAGCCTGGTAC ATCTGGATTCACCTTCAGTAACTATGGCATGCACTG
CAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATC GGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTGGG
TACGAAGCAGCCACCAGGGCCACTGGTATCCCAGC TGGCAGCTATATGGTTTGATGCAAGTGATAAATACT
CAGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCAC ATGCAGACGCCGTGAAGGGCCGATTCACCATCTCCA
NA
TCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGC GAGACAACTCCAAGAACACGCTGTATCTGCAAATG
AGTTTATTACTGTCAGCAGTATCAGCACTGGCCTCT AACAGCCTGAGAGCCGAGGACACGGCTGTGTATTA

n f 9) CACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA

f 9) n CGACTACTGGGGCCAGGGAACCCTGGTCACCGTGTC
cp o n.) PI TAGT
(SEQ ID NO: 781) (SEQ ID NO: 782) o oe 'a oe cA
oe EIVMTQ SP ATL SVSP GERATL SCRASQ SVSRHLAWYQ QVQLVE SGGGVVQPGRSLRL
SCAASGFTFSNYGMHW
QKP GQAPRLLIYEAATRATGIP ARF S GS GS GTEFTL TI S VRQAP GE GLEWVAAIWFD
ASDKYYADAVKGRFTI SR
AA SLQSEDFAVYYCQQYQHWPLTFGGGTKVEIK

YWGQGTLVTVSS
n.) o (SEQ ID NO: 783) (SEQ ID NO: 784) oe i-J
GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGT
c,.) --.1 GTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGG CCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGC
o --.1 GCCAGTCAGAGTGTTTTCAGCCACTTAGCCTGGTAC ATCTGGATTCACCTTCCAGAACTATGGCATGCACTG
CAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATC GGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTGGG
TACGAAGCAGCCACCAGGGCCACTGGTATCCCAGC TGGCAGCTATATGGTTTGATGCGTCTGACAAATACT
CAGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCAC ATGCAGACGCCGTGAAGGGCCGATTCACCATCTCCA
NA
TCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGC GAGACAACTCCAAGAACACGCTGTATCTGCAAATG
AGTTTATTACTGTCAGCAGTATCAGAACTGGCCTCT AACAGCCTGAGAGCCGAGGACACGGCTGTGTATTA
CACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA CTGTGCGAGAGATCTTGCGATTTTTGGAGTGGTCCC
CGACTACTGGGGCCAGGGAACCCTGGTCACCGTGTC
TAGT
p (SEQ ID NO: 785) (SEQ ID NO: 786) .
L.
EIVMTQ SP ATL SVSPGERATL SCRASQSVFSHLAWYQQ QVQLVESGGGVVQPGRSLRL
SCAASGFTFQNYGMHW "
, ,- KPGQAPRLLIYEAATRATGIPARFSGSGSGTEFTLTISSL
VRQAPGEGLEWVAAIWFDASDKYYADAVKGRFTISR .
o N, '1 o AA QSEDFAVYYCQQYQNWPLTFGGGTKVEIK
DNSKNTLYLQMNSLRAEDTAVYYCARDLAIFGVVPD
PI YWGQGTLVTVSS
(SEQ ID NO: 787) (SEQ ID NO: 788) , L.
, GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGT
GTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGG CCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGC
GCCAGTCAGAGTGTTTTCAGCCACTTAGCCTGGTAC ATCTGGATTCACCTTCCAGAACTATGGCATGCACTG
CAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATC GGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTGGG
TACGAAGCAGCCACCAGGGCCACTGGTATCCCAGC TGGCAGCTATATGGTTTGATGCGTCTGACAAATACT
CAGGGTCAGTGGCAGTGGGTCTGGGACAGAGTTCA ATGCAGACGCCGTGAAGGGCCGATTCACCATCTCCA
NA
CTCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTG GAGACAACTCCAAGAACACGCTGTATCTGCAAATG
CAGTTTATTACTGTCAGCAGTATCAGAACTGGCCTC AACAGCCTGAGAGCCGAGGACACGGCTGTGTATTA

n ,- TCACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA

o `z.
CGACTACTGGGGCCAGGGAACCCTGGTCACCGTGTC
cp o n.) PI TAGT
(SEQ ID NO: 789) (SEQ ID NO: 790) o oe 'a oe cA
oe EIVMTQ SP ATL SVSPGERATLSCRASQSVFSHLAWYQQ QVQLVESGGGVVQPGRSLRL
SCAASGFTFQNYGMHW
KP GQAPRLLIYEAATRAT GIP ARVS GS GS GTEFTL TI S S VRQAP GE GLEWVAAIWFD
ASDKYYADAVKGRFTI SR
AA LQSEDFAVYYCQQYQNWPLTFGGGTKVEIK

YWGQGTLVTVSS
n.) o (SEQ ID NO: 791) (SEQ ID NO: 792) oe i-J
GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGT
c,.) --.1 GTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGG CCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGC
o --.1 GCCAGTCAGAGTGTTCTGAGTCACTTAGCCTGGTAC ATCTGGATTCACCTTCCAGAACTATGGCATGCACTG
CAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATC GGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTGGG
TACGAAGCAGCCACCAGGGCCACTGGTATCCCAGC TGGCAGCTATATGGTTTGATGCGTCTGACAAATACT
CAGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCAC ATGCAGACGCCGTGAAGGGCCGATTCACCATCTCCA
NA
TCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGC GAGACAACTCCAAGAACACGCTGTATCTGCAAATG
AGTTTATTACTGTCAGCAGTATCAGCAGTGGCCTCT AACAGCCTGAGAGCCGAGGACACGGCTGTGTATTA
CACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA CTGTGCGAGAGATCTTGCGATTTTTGGAGTGGTCCC
CGACTACTGGGGCCAGGGAACCCTGGTCACCGTGTC
TAGT
p (SEQ ID NO: 793) (SEQ ID NO: 793) .
L.
EIVMTQ SP ATL SV SP GERATL SCRASQ SVL SHL AWYQ QVQLVESGGGVVQPGRSLRL
SCAASGFTFQNYGMHW "
, QKP GQAPRLLIYEAATRATGIP ARF S GS GS GTEFTL TI S VRQAP GE GLEWVAAIWFD
ASDKYYADAVKGRFTI SR .
N, n o AA SLQSEDFAVYYCQQYQQWPLTFGGGTKVEIK
DNSKNTLYLQMNSLRAEDTAVYYCARDLAIFGVVPD
PI YWGQGTLVTVSS
(SEQ ID NO: 75) (SEQ ID NO: 796) , L.
, GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGT
GTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGG CCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGC
GCCAGTCAGAGTGTTTTCAGCCACTTAGCCTGGTAC ATCTGGATTCACCTTCAGTAACTATGGCATGCACTG
CAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATC GGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTGGG
TACGAAGCAGCCACCAGGGCCACTGGTATCCCAGC TGGCAGCTATATGGTTTGATGCAAGTGATAAATACT
CAGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCAC ATGCAGACGCCGTGAAGGGCCGATTCACCATCTCCA
NA
TCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGC GAGACAACTCCAAGAACACGCTGTATCTGCAAATG
AGTTTATTACTGTCAGCAGTATCAGCAGTGGCCTCT AACAGCCTGAGAGCCGAGGACACGGCTGTGTATTA

n co CACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA

o n CGACTACTGGGGCCAGGGAACCCTGGTCACCGTGTC
cp o n.) PI TAGT
(SEQ ID NO: 797) (SEQ ID NO: 798) o oe 'a oe cA
oe EIVMTQ SP ATL SVSPGERATLSCRASQSVFSHLAWYQQ QVQLVE SGGGVVQPGRSLRL
SCAASGFTFSNYGMHW
KPGQAPRLLIYEAATRATGIPARFSGSGSGTEFTLTISSL VRQAPGEGLEWVAAIWFDASDKYYADAVKGRFTISR
AA QSEDFAVYYCQQYQQWPLTFGGGTKVEIK

YWGQGTLVTVSS
n.) o (SEQ ID NO: 799) (SEQ ID NO: 800) oe i-J
GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGT
c,.) --.1 GTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGG CCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGC
o --.1 GCCAGTCAGAGTGTTTTCAGCCACTTAGCCTGGTAC ATCTGGATTCACCTTCAGTAACTATGGCATGCACTG
CAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATC GGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTGGG
TACGAAGCAGCCACCAGGGCCACTGGTATCCCAGC TGGCAGCTATATGGTTTGATGCAAGTGATAAATACT
CAGGGTCAGTGGCAGTGGGTCTGGGACAGAGTTCA ATGCAGACGCCGTGAAGGGCCGATTCACCATCTCCA
NA
CTCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTG GAGACAACTCCAAGAACACGCTGTATCTGCAAATG
CAGTTTATTACTGTCAGCAGTATCAGCAGTGGCCTC AACAGCCTGAGAGCCGAGGACACGGCTGTGTATTA
TCACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA CTGTGCGAGAGATTTGGCGATTTTTGGAGTGGTCCC
CGACTACTGGGGCCAGGGAACCCTGGTCACCGTGTC
TAGT
p (SEQ ID NO: 801) (SEQ ID NO: 802) .
L.
EIVMTQ SP ATL SVSPGERATL SCRASQSVFSHLAWYQQ QVQLVE SGGGVVQPGRSLRL
SCAASGFTFSNYGMHW "
, co KP GQAPRLLIYEAATRAT GIP ARVS GS GS GTEFTL TI S S VRQAP GE
GLEWVAAIWFD ASDKYYADAVKGRFTI SR .
o N, AA LQSEDFAVYYCQQYQQWPLTFGGGTKVEIK
DNSKNTLYLQMNSLRAEDTAVYYCARDLAIFGVVPD
PI YWGQGTLVTVSS
(SEQ ID NO: 803) (SEQ ID NO: 804) , L.
, GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGT
GTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGG CCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGC
GCCAGTCAGAGTGTTCAGAGCCACTTAGCCTGGTAC ATCTGGATTCACCTTCAGTAACTATGGCATGCACTG
CAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATC GGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTGGG
TACGAAGCAGCCACCAGGGCCACTGGTATCCCAGC TGGCAGCTATATGGTTTGATGCAAGTGATAAATACT
CAGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCAC ATGCAGACGCCGTGAAGGGCCGATTCACCATCTCCA
NA
TCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGC GAGACAACTCCAAGAACACGCTGTATCTGCAAATG
AGTTTATTACTGTCAGCAGTATCAGAACTGGCCTCT AACAGCCTGAGAGCCGAGGACACGGCTGTGTATTA

n CACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA CTGTGCGAGAGATATTGCGATTTTTGGAGTGGTCCC

f e) f el CGACTACTGGGGCCAGGGAACCCTGGTCACCGTGTC
cp o n.) PI TAGT
(SEQ ID NO: 805) (SEQ ID NO: 806) o oe 'a oe cA
oe EIVMTQ SP ATL SVSPGERATL SCRASQSVQSHLAWYQ QVQLVE SGGGVVQPGRSLRL
SCAASGFTFSNYGMHW
QKP GQAPRLLIYEAATRATGIP ARF S GS GS GTEFTL TI S VRQAP GE GLEWVAAIWFD
ASDKYYADAVKGRFTI SR
AA SLQSEDFAVYYCQQYQNWPLTFGGGTKVEIK

WGQGTLVTVSS
n.) o (SEQ ID NO: 807) (SEQ ID NO: 808) oe i-J
GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGT
c,.) --.1 GTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGG CCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGC
o --.1 GCCAGTCAGAGTGTTAGTAGCCACTTAGCCTGGTAC ATCTGGATTCACCTTCAGTAACTATGGCATGCACTG
CAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATC GGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTGGG
TACGAAGCAGCCACCAGGGCCACTGGTATCCCAGC TGGCAGCTATATGGTTTGATGCAAGTGATAAATACT
CAGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCAC ATGCAGACGCCGTGAAGGGCCGATTCACCATCTCCA
NA
TCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGC GAGACAACTCCAAGAACACGCTGTATCTGCAAATG
AGTTTATTACTGTCAGCAGTATCAGCAGTGGCCTCT AACAGCCTGAGAGCCGAGGACACGGCTGTGTATTA
CACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA CTGTGCGAGAGATATTGCGATTTTTGGAGTGGTCCC
CGACTACTGGGGCCAGGGAACCCTGGTCACCGTGTC
TAGT
p (SEQ ID NO: 809) (SEQ ID NO: 810) .
L.
EIVMTQ SP ATL SVSPGERATL SCRASQSVS SHLAWYQQ QVQLVE SGGGVVQPGRSLRL
SCAASGFTFSNYGMHW "
, .7r KPGQAPRLLIYEAATRATGIPARFSGSGSGTEFTLTISSL
VRQAPGEGLEWVAAIWFDASDKYYADAVKGRFTISR .
.7r N, n o AA QSEDFAVYYCQQYQQWPLTFGGGTKVEIK
DNSKNTLYLQMNSLRAEDTAVYYCARDIAIFGVVPDY
PI WGQGTLVTVSS
(SEQ ID NO: 811) (SEQ ID NO: 812) , L.
, GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGT
GTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGG CCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGC
GCCAGTCAGAGTGTTTTCACGCACTTAGCCTGGTAC ATCTGGATTCACCTTCAGTAACTATGGCATGCACTG
CAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATC GGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTGGG
TACGAAGCAGCCACCAGGGCCACTGGTATCCCAGC TGGCAGCTATATGGTTTGATGCAAGTGATAAATACT
CAGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCAC ATGCAGACGCCGTGAAGGGCCGATTCACCATCTCCA
NA
TCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGC GAGACAACTCCAAGAACACGCTGTATCTGCAAATG
AGTTTATTACTGTCAGCAGTATAACAACTGGCCTCT AACAGCCTGAGAGCCGAGGACACGGCTGTGTATTA

n o CACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA

,-'91 CGACTACTGGGGCCAGGGAACCCTGGTCACCGTGTC
cp o n.) PI TAGT
(SEQ ID NO: 813) (SEQ ID NO: 814) o oe 'a oe cA
oe EIVMTQ SP ATL SV SP GERATL SCRASQ SVFTHL AWYQ QVQLVE SGGGVVQPGRSLRL
SCAASGFTFSNYGMHW
QKP GQAPRLLIYEAATRATGIP ARF S GS GS GTEFTL TI S VRQAP GE GLEWVAAIWFD
ASDKYYADAVKGRFTI SR
AA SLQSEDFAVYYCQQYNNWPLTFGGGTKVEIK

YWGQGTLVTVSS
n.) o (SEQ ID NO: 815) (SEQ ID NO: 816) oe i-J
GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGT
c,.) --.1 GTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGG CCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGC
o --.1 GCCAGTCAGAGTGTTTTCACGCACTTAGCCTGGTAC ATCTGGATTCACCTTCAGTAACTATGGCATGCACTG
CAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATC GGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTGGG
TACGAAGCAGCCACCAGGGCCACTGGTATCCCAGC TGGCAGCTATATGGTTTGATGCAAGTGATAAATACT
CAGGGTCAGTGGCAGTGGGTCTGGGACAGAGTTCA ATGCAGACGCCGTGAAGGGCCGATTCACCATCTCCA
NA
CTCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTG GAGACAACTCCAAGAACACGCTGTATCTGCAAATG
CAGTTTATTACTGTCAGCAGTATAACAACTGGCCTC AACAGCCTGAGAGCCGAGGACACGGCTGTGTATTA
TCACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA CTGTGCGAGAGATTTGGCGATTTTTGGAGTGGTCCC
CGACTACTGGGGCCAGGGAACCCTGGTCACCGTGTC
TAGT
p (SEQ ID NO: 817) (SEQ ID NO: 818) .
L.
EIVMTQ SP ATL SV SP GERATL SCRASQ SVFTHL AWYQ QVQLVE SGGGVVQPGRSLRL
SCAASGFTFSNYGMHW "
, o QKP GQAPRLLIYEAATRATGIP ARVS GS GS
GTEFTL TI S VRQAP GE GLEWVAAIWFD ASDKYYADAVKGRFTI SR .
N, AA SLQSEDFAVYYCQQYNNWPLTFGGGTKVEIK
DNSKNTLYLQMNSLRAEDTAVYYCARDLAIFGVVPD
PI YWGQGTLVTVSS
(SEQ ID NO: 819) (SEQ ID NO: 820) , L.
, GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGT
GTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGG CCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGC
GCCAGTCAGAGTGTTTTTGAACACTTAGCCTGGTAC ATCTGGATTCACCTTCAGTAACTATGGCATGCACTG
CAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATC GGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTGGG
TACGAAGCAGCCACCAGGGCCACTGGTATCCCAGC TGGCAGCTATATGGTTTGATGCAAGTGATAAATACT
CAGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCAC ATGCAGACGCCGTGAAGGGCCGATTCACCATCTCCA
NA
TCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGC GAGACAACTCCAAGAACACGCTGTATCTGCAAATG
AGTTTATTACTGTCAGCAGTATAACAACTGGCCTCT AACAGCCTGAGAGCCGAGGACACGGCTGTGTATTA

n CACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA CTGTGCGAGAGATTTGGCGATTTTTGGAGTGGTCCC

,-n CGACTACTGGGGCCAGGGAACCCTGGTCACCGTGTC
cp o n.) PI TAGT
(SEQ ID NO: 821) (SEQ ID NO: 822) o oe 'a oe cA
oe EIVMTQ SP ATL SV SP GERATL SCRASQ SVFEHL AWYQ QVQLVE SGGGVVQPGRSLRL
SCAASGFTFSNYGMHW
QKP GQAPRLLIYEAATRATGIP ARF S GS GS GTEFTL TI S VRQAP GE GLEWVAAIWFD
ASDKYYADAVKGRFTI SR
AA SLQSEDFAVYYCQQYNNWPLTFGGGTKVEIK

YWGQGTLVTVSS
n.) o (SEQ ID NO: 823) (SEQ ID NO: 824) oe i-J
GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGT
c,.) --.1 GTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGG CCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGC
o --.1 GCCAGTCAGAGTGTTGAACAGCACTTAGCCTGGTAC ATCTGGATTCACCTTCAGTAACTATGGCATGCACTG
CAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATC GGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTGGG
TACGAAGCAGCCACCAGGGCCACTGGTATCCCAGC TGGCAGCTATATGGTTTGATGCAAGTGATAAATACT
CAGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCAC ATGCAGACGCCGTGAAGGGCCGATTCACCATCTCCA
NA
TCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGC GAGACAACTCCAAGAACACGCTGTATCTGCAAATG
AGTTTATTACTGTCAGCAGTATAACAACTGGCCTCT AACAGCCTGAGAGCCGAGGACACGGCTGTGTATTA
CACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA CTGTGCGAGAGATTTGGCGATTTTTGGAGTGGTCCC
CGACTACTGGGGCCAGGGAACCCTGGTCACCGTGTC
TAGT
p (SEQ ID NO: 825) (SEQ ID NO: 826) .
L.
EIVMTQ SP ATL SV SPGERATL SCRASQ SVEQHLAWYQ QVQLVE SGGGVVQPGRSLRL
SCAASGFTFSNYGMHW "
, o, QKP GQAPRLLIYEAATRATGIP ARF S GS GS GTEFTL TI S VRQAP GE GLEWVAAIWFD
ASDKYYADAVKGRFTI SR .
N, n o AA SLQSEDFAVYYCQQYNNWPLTFGGGTKVEIK
DNSKNTLYLQMNSLRAEDTAVYYCARDLAIFGVVPD
PI YWGQGTLVTVSS
(SEQ ID NO: 827) (SEQ ID NO: 828) , L.
, GAAATAGTGATGACGCAGTCTCCGGCCACCCTGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGT
GTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGG CCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGC
GCCAGTCAGAGTGTTCATAGCCACTTAGCCTGGTAC ATCTGGATTCACCTTCAGTAACTATGGCATGCACTG
CAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATC GGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTGGG
TACGAAGCAGCCACCAGGGCCACTGGTATCCCAGC TGGCAGCTATATGGTTTGATGCAAGTGATAAATACT
CAGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCAC ATGCAGACGCCGTGAAGGGCCGATTCACCATCTCCA
NA
TCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGC GAGACAACTCCAAGAACACGCTGTATCTGCAAATG
AGTTTATTACTGTCAGCAGTATAACCAGTGGCCTCT AACAGCCTGAGAGCCGAGGACACGGCTGTGTATTA

n N CACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA

n CGACTACTGGGGCCAGGGAACCCTGGTCACCGTGTC
cp o n.) PI TAGT
(SEQ ID NO: 829) (SEQ ID NO: 830) o oe 'a oe cA
oe EIVMTQ SP ATL SVSPGERATL SCRASQSVHSHLAWYQ QVQLVE SGGGVVQPGRSLRL
SCAASGFTFSNYGMHW
QKP GQAPRLLIYEAATRATGIP ARF S GS GS GTEFTL TI S VRQAP GE GLEWVAAIWFD
ASDKYYADAVKGRFTI SR
AA SLQSEDFAVYYCQQYNQWPLTFGGGTKVEIK

YWGQGTLVTVSS
n.) o (SEQ ID NO: 831) (SEQ ID NO: 832) oe i-J
GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGT
c,.) --.1 GTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGG CCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGC
o --.1 GCCAGTCAGAGTGTTCATCATCACTTAGCCTGGTAC ATCTGGATTCACCTTCAGTAACTATGGCATGCACTG
CAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATC GGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTGGG
TACGAAGCAGCCACCAGGGCCACTGGTATCCCAGC TGGCAGCTATATGGTTTGATGCAAGTGATAAATACT
CAGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCAC ATGCAGACGCCGTGAAGGGCCGATTCACCATCTCCA
NA
TCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGC GAGACAACTCCAAGAACACGCTGTATCTGCAAATG
AGTTTATTACTGTCAGCAGTATAACCAGTGGCCTCT AACAGCCTGAGAGCCGAGGACACGGCTGTGTATTA
CACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA CTGTGCGAGAGATTTGGCGATTTTTGGAGTGGTCCC
CGACTACTGGGGCCAGGGAACCCTGGTCACCGTGTC
TAGT
p (SEQ ID NO: 833) (SEQ ID NO: 834) .
L.
EIVMTQ SP ATL SVSPGERATL SCRASQSVHHHLAWYQ QVQLVE SGGGVVQPGRSLRL
SCAASGFTFSNYGMHW "
, co QKP GQAPRLLIYEAATRATGIP ARF S GS GS GTEFTL TI S VRQAP GE GLEWVAAIWFD
ASDKYYADAVKGRFTI SR .
f el o AA SLQSEDFAVYYCQQYNQWPLTFGGGTKVEIK
DNSKNTLYLQMNSLRAEDTAVYYCARDLAIFGVVPD
PI YWGQGTLVTVSS
(SEQ ID NO: 835) (SEQ ID NO: 836) , L.
, GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGT
GTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGG CCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGC
GCCAGTCAGAGTGTTCATAGCCACTTAGCCTGGTAC ATCTGGATTCACCTTCAGTAACTATGGCATGCACTG
CAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATC GGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTGGG
TACGAAGCAGCCACCAGGGCCACTGGTATCCCAGC TGGCAGCTATATGGTTTGATGCAAGTGATAAATACT
CAGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCAC ATGCAGACGCCGTGAAGGGCCGATTCACCATCTCCA
NA
TCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGC GAGACAACTCCAAGAACACGCTGTATCTGCAAATG
AGTTTATTACTGTCAGCAGTATAACAACTGGCCTCT AACAGCCTGAGAGCCGAGGACACGGCTGTGTATTA

n .7r CACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA

,-fl CGACTACTGGGGCCAGGGAACCCTGGTCACCGTGTC
cp o n.) PI TAGT
(SEQ ID NO: 837) (SEQ ID NO: 838) o oe 'a oe cA
oe EIVMTQ SP ATL SVSPGERATL SCRASQSVHSHLAWYQ QVQLVE SGGGVVQPGRSLRL
SCAASGFTFSNYGMHW
QKP GQAPRLLIYEAATRATGIP ARF S GS GS GTEFTL TI S VRQAP GE GLEWVAAIWFD
ASDKYYADAVKGRFTI SR
AA SLQSEDFAVYYCQQYNNWPLTFGGGTKVEIK

YWGQGTLVTVSS
n.) o (SEQ ID NO: 839) (SEQ ID NO: 840) oe i-J
GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGT
c,.) --.1 GTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGG CCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGC
o --.1 GCCAGTCAGAGTGTTGATGTCAACTTAGCCTGGTAC ATCTGGATTCACCTTCAGTAACTATGGCATGCACTG
CAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATC GGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTGGG
TACGAAGCAGCCACCAGGGCCACTGGTATCCCAGC TGGCAGCTATATGGTTTGATGCAAGTGATAAATACT
CAGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCAC ATGCAGACGCCGTGAAGGGCCGATTCACCATCTCCA
NA
TCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGC GAGACAACTCCAAGAACACGCTGTATCTGCAAATG
AGTTTATTACTGTCAGCAGTATAACCAGTGGCCTCT AACAGCCTGAGAGCCGAGGACACGGCTGTGTATTA
CACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA CTGTGCGAGAGATTTGGCGATTTTTGGAGTGGTCCC
CGACTACTGGGGCCAGGGAACCCTGGTCACCGTGTC
TAGT
p (SEQ ID NO: 841) (SEQ ID NO: 842) .
L.
EIVMTQ SP ATL SVSPGERATL SCRASQSVDVNLAWYQ QVQLVE SGGGVVQPGRSLRL
SCAASGFTFSNYGMHW "
, N QKP GQAPRLLIYEAATRATGIP ARF S GS GS GTEFTL TI S VRQAP GE GLEWVAAIWFD
ASDKYYADAVKGRFTI SR .
f el o AA SLQSEDFAVYYCQQYNQWPLTFGGGTKVEIK
DNSKNTLYLQMNSLRAEDTAVYYCARDLAIFGVVPD
PI YWGQGTLVTVSS
(SEQ ID NO: 834) (SEQ ID NO: 844) , L.
, GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGT
GTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGG CCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGC
GCCAGTCAGAGTGTTGATGTCCACTTAGCCTGGTAC ATCTGGATTCACCTTCAGTAACTATGGCATGCACTG
CAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATC GGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTGGG
TACGAAGCAGCCACCAGGGCCACTGGTATCCCAGC TGGCAGCTATATGGTTTGATGCAAGTGATAAATACT
CAGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCAC ATGCAGACGCCGTGAAGGGCCGATTCACCATCTCCA
NA
TCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGC GAGACAACTCCAAGAACACGCTGTATCTGCAAATG
AGTTTATTACTGTCAGCAGTATAACCAGTGGCCTCT AACAGCCTGAGAGCCGAGGACACGGCTGTGTATTA

n ,- CACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA

.7r fl CGACTACTGGGGCCAGGGAACCCTGGTCACCGTGTC
cp o n.) PI TAGT
(SEQ ID NO: 845) (SEQ ID NO: 846) o oe 'a oe cA
oe EIVMTQ SP ATL SVSPGERATL SCRASQSVDVHLAWYQ QVQLVE SGGGVVQPGRSLRL
SCAASGFTFSNYGMHW
QKP GQAPRLLIYEAATRATGIP ARF S GS GS GTEFTL TI S VRQAP GE GLEWVAAIWFD
ASDKYYADAVKGRFTI SR
AA SLQSEDFAVYYCQQYNQWPLTFGGGTKVEIK

YWGQGTLVTVSS
n.) o (SEQ ID NO: 847) (SEQ ID NO: 848) oe i-J
GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGT
c,.) --.1 GTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGG CCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGC
o --.1 GCCAGTCAGAGTGTTTTTGAACACTTAGCCTGGTAC ATCTGGATTCACCTTCAGTAACTATGGCATGCACTG
CAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATC GGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTGGG
TACGAAGCAGCCACCAGGGCCACTGGTATCCCAGC TGGCAGCTATATGGTTTGATGCAAGTGATAAATACT
CAGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCAC ATGCAGACGCCGTGAAGGGCCGATTCACCATCTCCA
NA
TCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGC GAGACAACTCCAAGAACACGCTGTATCTGCAAATG
AGTTTATTACTGTCAGCAGTATAACAACTGGCCTCT AACAGCCTGAGAGCCGAGGACACGGCTGTGTATTA
CACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA CTGTGCGAGAGATATTGCGATTTTTGGAGTGTTTCC
CGACTACTGGGGCCAGGGAACCCTGGTCACCGTGTC
TAGT
p (SEQ ID NO: 849) (SEQ ID NO: 850) .
L.
EIVMTQ SP ATL SV SP GERATL SCRASQ SVFEHL AWYQ QVQLVE SGGGVVQPGRSLRL
SCAASGFTFSNYGMHW "
, QKP GQAPRLLIYEAATRATGIP ARF S GS GS GTEFTL TI S VRQAP GE GLEWVAAIWFD
ASDKYYADAVKGRFTI SR .
o N, '1 o AA SLQSEDFAVYYCQQYNNWPLTFGGGTKVEIK
DNSKNTLYLQMNSLRAEDTAVYYCARDIAIFGVFPDY
PI WGQGTLVTVSS
(SEQ ID NO: 851) (SEQ ID NO: 852) , L.
, GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGT
GTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGG CCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGC
GCCAGTCAGAGTGTTTTTGAACACTTAGCCTGGTAC ATCTGGATTCACCTTCAGTAACTATGGCATGCACTG
CAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATC GGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTGGG
TACGAAGCAGCCACCAGGGCCACTGGTATCCCAGC TGGCAGCTATATGGTTTGATGCAAGTGATAAATACT
CAGGGTCAGTGGCAGTGGGTCTGGGACAGAGTTCA ATGCAGACGCCGTGAAGGGCCGATTCACCATCTCCA
NA
CTCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTG GAGACAACTCCAAGAACACGCTGTATCTGCAAATG
CAGTTTATTACTGTCAGCAGTATAACAACTGGCCTC AACAGCCTGAGAGCCGAGGACACGGCTGTGTATTA

n TCACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA CTGTGCGAGAGATATTGCGATTTTTGGAGTGTTTCC

o `z.
CGACTACTGGGGCCAGGGAACCCTGGTCACCGTGTC
cp o n.) PI TAGT
(SEQ ID NO: 853) (SEQ ID NO: 854) o oe 'a oe cA
oe EIVMTQ SP ATL SV SP GERATL SCRASQ SVFEHL AWYQ QVQLVE SGGGVVQPGRSLRL
SCAASGFTFSNYGMHW
QKP GQAPRLLIYEAATRATGIP ARVS GS GS GTEFTL TI S VRQAP GE GLEWVAAIWFD
ASDKYYADAVKGRFTI SR
AA SLQSEDFAVYYCQQYNNWPLTFGGGTKVEIK

WGQGTLVTVSS
n.) o (SEQ ID NO: 855) (SEQ ID NO: 856) oe i-J
GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGT
c,.) --.1 GTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGG CCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGC
o --.1 GCCAGTCAGAGTGTTTTCGAACACTTAGCCTGGTAC ATCTGGATTCACCTTCAGTAACTATGGCATGCACTG
CAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATC GGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTGGG
TACGAAGCAGCCACCAGGGCCACTGGTATCCCAGC TGGCAGCTATATGGTTTGATGCAAGTGATAAATACT
CAGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCAC ATGCAGACGCCGTGAAGGGCCGATTCACCATCTCCA
NA
TCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGC GAGACAACTCCAAGAACACGCTGTATCTGCAAATG
AGTTTATTACTGTCAGCAGTATAACCAGTGGCCTCT AACAGCCTGAGAGCCGAGGACACGGCTGTGTATTA
CACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA CTGTGCGAGAGATATTGCGATTTTTGGAGTGGTCCC
CGACTACTGGGGCCAGGGAACCCTGGTCACCGTGTC
TAGT
p (SEQ ID NO: 857) (SEQ ID NO: 858) .
L.
EIVMTQ SP ATL SV SP GERATL SCRASQ SVFEHL AWYQ QVQLVE SGGGVVQPGRSLRL
SCAASGFTFSNYGMHW "
, in QKP GQAPRLLIYEAATRATGIP ARF S GS GS GTEFTL TI S VRQAP GE GLEWVAAIWFD
ASDKYYADAVKGRFTI SR .
N, n o AA SLQSEDFAVYYCQQYNQWPLTFGGGTKVEIK
DNSKNTLYLQMNSLRAEDTAVYYCARDIAIFGVVPDY
PI WGQGTLVTVSS
(SEQ ID NO: 859) (SEQ ID NO: 860) , L.
, GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGT
GTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGG CCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGC
GCCAGTCAGAGTGTTCTGGAACACTTAGCCTGGTAC ATCTGGATTCACCTTCAGTAACTATGGCATGCACTG
CAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATC GGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTGGG
TACGAAGCAGCCACCAGGGCCACTGGTATCCCAGC TGGCAGCTATATGGTTTGATGCAAGTGATAAATACT
CAGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCAC ATGCAGACGCCGTGAAGGGCCGATTCACCATCTCCA
NA
TCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGC GAGACAACTCCAAGAACACGCTGTATCTGCAAATG
AGTTTATTACTGTCAGCAGTATAACAACTGGCCTCT AACAGCCTGAGAGCCGAGGACACGGCTGTGTATTA

n f 9) CACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA

.7r n CGACTACTGGGGCCAGGGAACCCTGGTCACCGTGTC
cp o n.) PI TAGT
(SEQ ID NO: 861) (SEQ ID NO: 862) o oe 'a oe cA
oe EIVMTQ SP ATL SV SP GERATL SCRASQ SVLEHLAWYQ QVQLVE SGGGVVQPGRSLRL
SCAASGFTFSNYGMHW
QKP GQAPRLLIYEAATRATGIP ARF S GS GS GTEFTL TI S VRQAP GE GLEWVAAIWFD
ASDKYYADAVKGRFTI SR
AA SLQSEDFAVYYCQQYNNWPLTFGGGTKVEIK

WGQGTLVTVSS
n.) o (SEQ ID NO: 863) (SEQ ID NO: 864) oe i-J
GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGT
c,.) --.1 GTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGG CCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGC
o --.1 GCCAGTCAGAGTGTTGATAGACACTTAGCCTGGTAC ATCTGGATTCACCTTCAGTAACTATGGCATGCACTG
CAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATC GGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTGGG
TACGAAGCAGCCACCAGGGCCACTGGTATCCCAGC TGGCAGCTATATGGTTTGATGCAAGTGATAAATACT
CAGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCAC ATGCAGACGCCGTGAAGGGCCGATTCACCATCTCCA
NA
TCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGC GAGACAACTCCAAGAACACGCTGTATCTGCAAATG
AGTTTATTACTGTCAGCAGTATAACCAGTGGCCTCT AACAGCCTGAGAGCCGAGGACACGGCTGTGTATTA
CACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA CTGTGCGAGAGATATTGCGATTTTTGGAGTGTTTCC
CGACTACTGGGGCCAGGGAACCCTGGTCACCGTGTC
TAGT
p (SEQ ID NO: 865) (SEQ ID NO: 866) .
L.
EIVMTQ SP ATL SV SP GERATL SCRASQ SVDRHLAWYQ QVQLVE SGGGVVQPGRSLRL
SCAASGFTFSNYGMHW "
, f e) QKP GQAPRLLIYEAATRATGIP ARF S GS GS GTEFTL TI S VRQAP GE GLEWVAAIWFD
ASDKYYADAVKGRFTI SR .
N, 'el o AA SLQSEDFAVYYCQQYNQWPLTFGGGTKVEIK
DNSKNTLYLQMNSLRAEDTAVYYCARDIAIFGVFPDY
PI WGQGTLVTVSS
(SEQ ID NO: 867) (SEQ ID NO: 868) , L.
, GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGT
GTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGG CCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGC
GCCAGTCAGAGTGTTAACCGGCACTTAGCCTGGTAC ATCTGGATTCACCTTCAGTAACTATGGCATGCACTG
CAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATC GGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTGGG
TACGAAGCAGCCACCAGGGCCACTGGTATCCCAGC TGGCAGCTATATGGTTTGATGCAAGTGATAAATACT
CAGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCAC ATGCAGACGCCGTGAAGGGCCGATTCACCATCTCCA
NA
TCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGC GAGACAACTCCAAGAACACGCTGTATCTGCAAATG
AGTTTATTACTGTCAGCAGTATCAGCAGTGGCCTCT AACAGCCTGAGAGCCGAGGACACGGCTGTGTATTA

n N CACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA

,-fl CGACTACTGGGGCCAGGGAACCCTGGTCACCGTGTC
cp o n.) PI TAGT
(SEQ ID NO: 869) (SEQ ID NO: 870) o oe 'a oe cA
oe EIVMTQSPATLSVSPGERATLSCRASQSVNRHLAWYQ QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMHW
QKPGQAPRLLIYEAATRATGIPARFSGSGSGTEFTLTIS VRQAPGEGLEWVAAIWFDASDKYYADAVKGRFTISR
AA SLQSEDFAVYYCQQYQQWPLTFGGGTKVEIK

WGQGTLVTVSS
n.) o (SEQ ID NO: 871) (SEQ ID NO: 872) oe i-J
GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGT
c,.) --.1 GTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGG CCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGC
o --.1 GCCAGTCAGAGTGTTAACGTACACTTAGCCTGGTAC ATCTGGATTCACCTTCAGTAACTATGGCATGCACTG
CAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATC GGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTGGG
TACCAGGCAGCCACCAGGGCCACTGGTATCCCAGCC TGGCAGCTATATGGTTTGATGCAAGTGATAAATACT
AGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCACT ATGCAGACGCCGTGAAGGGCCGATTCACCATCTCCA
NA
CTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGCA GAGACAACTCCAAGAACACGCTGTATCTGCAAATG
GTTTATTACTGTCAGCAGTATAACCAGTGGCCTCTC AACAGCCTGAGAGCCGAGGACACGGCTGTGTATTA
ACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA
CTGTGCGAGAGATATTGCGATTTTTGGAGTGTTTCC
CGACTACTGGGGCCAGGGAACCCTGGTCACCGTGTC
TAGT
p (SEQ ID NO: 873) (SEQ ID NO: 874) .
L.
EIVMTQSPATLSVSPGERATLSCRASQSVNVHLAWYQ QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMHW
"
, ,- QKPGQAPRLLIYQAATRATGIPARFSGSGSGTEFTLTIS
VRQAPGEGLEWVAAIWFDASDKYYADAVKGRFTISR .
N, n o AA SLQSEDFAVYYCQQYNQWPLTFGGGTKVEIK
DNSKNTLYLQMNSLRAEDTAVYYCARDIAIFGVFPDY
PI WGQGTLVTVSS
(SEQ ID NO: 875) (SEQ ID NO: 876) , L.
, GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGT
GTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGG CCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGC
GCCAGTCAGAGTGTTCTGACGCACTTAGCCTGGTAC ATCTGGATTCACCTTCAGTAACTATGGCATGCACTG
CAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATC GGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTGGG
TACGAAGCAGCCACCAGGGCCACTGGTATCCCAGC TGGCAGCTATATGGTTTGATGCAAGTGATAAATACT
CAGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCAC ATGCAGACGCCGTGAAGGGCCGATTCACCATCTCCA
NA
TCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGC GAGACAACTCCAAGAACACGCTGTATCTGCAAATG
AGTTTATTACTGTCAGCAGTATCAGAACTGGCCTCT AACAGCCTGAGAGCCGAGGACACGGCTGTGTATTA

n CACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA CTGTGCGAGAGATATTGCGATTTTTGGAGTGATCCC

o n CGACTACTGGGGCCAGGGAACCCTGGTCACCGTGTC
cp o n.) PI TAGT
(SEQ ID NO: 877) (SEQ ID NO: 878) o oe 'a oe cA
oe EIVMTQ SP ATL SV SP GERATL SCRASQ SVLTHLAWYQ QVQLVE SGGGVVQPGRSLRL
SCAASGFTFSNYGMHW
QKP GQAPRLLIYEAATRATGIP ARF S GS GS GTEFTL TI S VRQAP GE GLEWVAAIWFD
ASDKYYADAVKGRFTI SR
AA SLQSEDFAVYYCQQYQNWPLTFGGGTKVEIK

WGQGTLVTVSS
n.) o (SEQ ID NO: 879) (SEQ ID NO: 880) oe i-J
GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGT
c,.) --.1 GTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGG CCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGC
o --.1 GCCAGTCAGAGTGTTCTGACGCACTTAGCCTGGTAC ATCTGGATTCACCTTCAGTAACTATGGCATGCACTG
CAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATC GGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTGGG
TACGAAGCAGCCACCAGGGCCACTGGTATCCCAGC TGGCAGCTATATGGTTTGATGCAAGTGATAAATACT
CAGGGTCAGTGGCAGTGGGTCTGGGACAGAGTTCA ATGCAGACGCCGTGAAGGGCCGATTCACCATCTCCA
NA
CTCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTG GAGACAACTCCAAGAACACGCTGTATCTGCAAATG
CAGTTTATTACTGTCAGCAGTATCAGAACTGGCCTC AACAGCCTGAGAGCCGAGGACACGGCTGTGTATTA
TCACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA CTGTGCGAGAGATATTGCGATTTTTGGAGTGATCCC
CGACTACTGGGGCCAGGGAACCCTGGTCACCGTGTC
TAGT
p (SEQ ID NO: 881) (SEQ ID NO: 882) .
L.
EIVMTQ SP ATL SV SP GERATL SCRASQ SVLTHLAWYQ QVQLVE SGGGVVQPGRSLRL
SCAASGFTFSNYGMHW "
, QKP GQAPRLLIYEAATRATGIP ARVS GS GS GTEFTL TI S VRQAP GE GLEWVAAIWFD
ASDKYYADAVKGRFTI SR .
o N, AA SLQSEDFAVYYCQQYQNWPLTFGGGTKVEIK
DNSKNTLYLQMNSLRAEDTAVYYCARDIAIFGVIPDY
PI WGQGTLVTVSS
(SEQ ID NO: 883) (SEQ ID NO: 884) , L.
, GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGT
GTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGG CCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGC
GCCAGTCAGAGTGTTAGCAGCAACTTAGCCTGGTAC ATCTGGATTCACCTTCAGTAACTATGGCATGCACTG
CAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATC GGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTGGG
TATGGTGCAGCCACCAGGGCCACTGGTATCCCAGCC TGGCAGCTATATGGTTTGATGCAAGTGATAAATACT
AGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCACT ATGCAGACGCCGTGAAGGGCCGATTCACCATCTCCA
NA
CTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGCA GAGACAACTCCAAGAACACGCTGTATCTGCAAATG
GTTTATTACTGTCAGCAGTATAATAACTGGCCTCTC AACAGCCTGAGAGCCGAGGACACGGCTGTGTATTA

n N ACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA CTGTGCGAGAGATTTGGCGATTTTTGGAGTGGTCCC

.7r n CGACTACTGGGGCCAGGGAACCCTGGTCACCGTGTC
cp o n.) PI TAGT
(SEQ ID NO: 885) (SEQ ID NO: 886) o oe 'a oe cA
oe EIVMTQ SP ATL SVSPGERATLSCRASQSVS SNLAWYQQ QVQLVE SGGGVVQPGRSLRL
SCAASGFTFSNYGMHW
KPGQAPRLLIYGAATRATGIPARFS GS GS GTEFTLTI S S VRQAP GE GLEWVAAIWFD
ASDKYYADAVKGRFTI SR
AA LQSEDFAVYYCQQYNNWPLTFGGGTKVEIK

YWGQGTLVTVSS
n.) o (SEQ ID NO: 887) (SEQ ID NO: 888) oe i-J
GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGT
c,.) --.1 GTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGG CCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGC
o --.1 GCCAGTCAGAGTGTTAGCAGCAACTTAGCCTGGTAC ATCTGGATTCACCTTCAGTAACTATGGCATGCACTG
CAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATC GGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTGGG
TATGGTGCAGCCACCAGGGCCACTGGTATCCCAGCC TGGCAGCTATATGGTTTGATGCAAGTGATAAATACT
AGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCACT ATGCAGACGCCGTGAAGGGCCGATTCACCATCTCCA
NA
CTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGCA GAGACAACTCCAAGAACACGCTGTATCTGCAAATG
GTTTATTACTGTCAGCAGTATAATAACTGGCCTCTC AACAGCCTGAGAGCCGAGGACACGGCTGTGTATTA
ACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA
CTGTGCGAGAGATCAGGCGATTTTTGGAGTGGTCCC
CGATTACTGGGGCCAGGGAACCCTGGTCACCGTGTC
TAGT
p (SEQ ID NO: 889) (SEQ ID NO: 890) .
L.
EIVMTQ SP ATL SVSPGERATL SCRASQSVS SNLAWYQQ QVQLVE SGGGVVQPGRSLRL
SCAASGFTFSNYGMHW "
, co KPGQAPRLLIYGAATRATGIPARFS GS GS GTEFTLTI S S VRQAP GE GLEWVAAIWFD
ASDKYYADAVKGRFTI SR .
.7r N, n o AA LQSEDFAVYYCQQYNNWPLTFGGGTKVEIK
DNSKNTLYLQMNSLRAEDTAVYYCARDQAIFGVVPD
PI YWGQGTLVTVSS
(SEQ ID NO: 891) (SEQ ID NO: 892) , L.
, GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGT
GTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGG CCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGC
GCCAGTCAGAGTGTTAGCAGCAACTTAGCCTGGTAC ATCTGGATTCACCTTCAGTAACTATGGCATGCACTG
CAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATC GGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTGGG
TATGGTGCAGCCACCAGGGCCACTGGTATCCCAGCC TGGCAGCTATATGGTTTGATGCAAGTGATAAATACT
AGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCACT ATGCAGACGCCGTGAAGGGCCGATTCACCATCTCCA
NA
CTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGCA GAGACAACTCCAAGAACACGCTGTATCTGCAAATG
GTTTATTACTGTCAGCAGTATAATAACTGGCCTCTC AACAGCCTGAGAGCCGAGGACACGGCTGTGTATTA

n ACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA CTGTGCGAGAGATATTGCGATTTTTGGAGTGGTCCC

.7r n CGACTACTGGGGCCAGGGAACCCTGGTCACCGTGTC
cp o n.) PI TAGT
(SEQ ID NO: 893) (SEQ ID NO: 894) o oe 'a oe cA
oe EIVMTQSPATL SVSPGERATLSCRASQSVSSNLAWYQQ QVQLVE SGGGVVQPGRSLRL SCAASGFTFSNYGMHW
KPGQAPRLLIYGAATRATGIPARFS GS GS GTEFTLTI S S VRQAP GE GLEWVAAIWFD
ASDKYYADAVKGRFTI SR
AA LQSEDFAVYYCQQYNNWPLTFGGGTKVEIK

WGQGTLVTVSS
n.) o (SEQ ID NO: 895) (SEQ ID NO: 896) oe i-J
GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGT
c,.) --.1 GTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGG CCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGC
o --.1 GCCAGTCAGAGTGTTAGCAGCAACTTAGCCTGGTAC ATCTGGATTCACCTTCAGTAACTATGGCATGCACTG
CAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATC GGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTGGG
TATGGTGCAGCCACCAGGGCCACTGGTATCCCAGCC TGGCAGCTATATGGTTTGATGCAAGTGATAAATACT
AGGGTCAGTGGCAGTGGGTCTGGGACAGAGTTCAC ATGCAGACGCCGTGAAGGGCCGATTCACCATCTCCA
NA
TCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGC GAGACAACTCCAAGAACACGCTGTATCTGCAAATG
AGTTTATTACTGTCAGCAGTATAATAACTGGCCTCT AACAGCCTGAGAGCCGAGGACACGGCTGTGTATTA
CACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA CTGTGCGAGAGATTTGGCGATTTTTGGAGTGGTCCC
CGACTACTGGGGCCAGGGAACCCTGGTCACCGTGTC
TAGT
p (SEQ ID NO: 897) (SEQ ID NO: 898) .
L.
EIVMTQSPATL SVSPGERATL SCRASQSVSSNLAWYQQ QVQLVE SGGGVVQPGRSLRL
SCAASGFTFSNYGMHW "
, N KP GQAPRLLIYGAATRATGIPARVS GS GS GTEFTL TI S S VRQAP GE GLEWVAAIWFD
ASDKYYADAVKGRFTI SR .
.7r N, AA LQSEDFAVYYCQQYNNWPLTFGGGTKVEIK
DNSKNTLYLQMNSLRAEDTAVYYCARDLAIFGVVPD
PI YWGQGTLVTVSS
(SEQ ID NO: 899) (SEQ ID NO: 900) , L.
, GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGT
GTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGG CCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGC
GCCAGTCAGAGTGTTAGCAGCAACTTAGCCTGGTAC ATCTGGATTCACCTTCAGTAACTATGGCATGCACTG
CAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATC GGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTGGG
TATGAAGCAGCCACCAGGGCCACTGGTATCCCAGCC TGGCAGCTATATGGTTTGATGCAAGTGATAAATACT
AGGGTCAGTGGCAGTGGGTCTGGGACAGAGTTCAC ATGCAGACGCCGTGAAGGGCCGATTCACCATCTCCA
NA
TCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGC GAGACAACTCCAAGAACACGCTGTATCTGCAAATG
AGTTTATTACTGTCAGCAGTATAATAACTGGCCTCT AACAGCCTGAGAGCCGAGGACACGGCTGTGTATTA

n c, CACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA

.7r `z.
CGATTACTGGGGCCAGGGAACCCTGGTCACCGTGTC
cp o n.) PI TAGT
(SEQ ID NO: 901) (SEQ ID NO: 902) o oe 'a oe cA
oe

68 EIVMTQSPATLSVSPGERATLSCRASQSVSSNLAWYQQ QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMHW
KPGQAPRLLIYEAATRATGIPARVSGSGSGTEFTLTISS VRQAPGEGLEWVAAIWFDASDKYYADAVKGRFTISR
AA LQSEDFAVYYCQQYNNWPLTFGGGTKVEIK

YWGQGTLVTVSS
n.) o (SEQ ID NO: 903) (SEQ ID NO: 904) oe i-J
GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGT
c,.) --.1 GTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGG CCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGC
o --.1 GCCAGTCAGAGTGTTGATGTTAACTTAGCCTGGTAC ATCTGGATTCACCTTCAGTAACTATGGCATGCACTG
CAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATC GGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTGGG
TACAACGCAGCCACCAGGGCCACTGGTATCCCAGCC TGGCAGCTATATGGTTTGATGCAAGTGATAAATACT
AGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCACT ATGCAGACGCCGTGAAGGGCCGATTCACCATCTCCA
NA
CTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGCA GAGACAACTCCAAGAACACGCTGTATCTGCAAATG
GTTTATTACTGTCAGCAGTATCAGAACTGGCCTCTC AACAGCCTGAGAGCCGAGGACACGGCTGTGTATTA
ACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA
CTGTGCGAGAGATTTGGCGATTTTTGGAGTGGTCCC
CGACTACTGGGGCCAGGGAACCCTGGTCACCGTGTC
TAGT
p (SEQ ID NO: 905) (SEQ ID NO: 906) .
L.
EIVMTQSPATLSVSPGERATLSCRASQSVDVNLAWYQ QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMHW
"
, in QKPGQAPRLLIYNAATRATGIPARFSGSGSGTEFTLTIS
VRQAPGEGLEWVAAIWFDASDKYYADAVKGRFTISR .
o N, '1 o AA SLQSEDFAVYYCQQYQNWPLTFGGGTKVEIK
DNSKNTLYLQMNSLRAEDTAVYYCARDLAIFGVVPD
PI YWGQGTLVTVSS
(SEQ ID NO: 907) (SEQ ID NO: 908) , L.
, GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGT
GTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGG CCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGC
GCCAGTCAGAGTGTTGATGTTAACTTAGCCTGGTAC ATCTGGATTCACCTTCAGTAACTATGGCATGCACTG
CAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATC GGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTGGG
TACAACGCAGCCACCAGGGCCACTGGTATCCCAGCC TGGCAGCTATATGGTTTGATGCAAGTGATAAATACT
AGGGTCAGTGGCAGTGGGTCTGGGACAGAGTTCAC ATGCAGACGCCGTGAAGGGCCGATTCACCATCTCCA
NA
TCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGC GAGACAACTCCAAGAACACGCTGTATCTGCAAATG
AGTTTATTACTGTCAGCAGTATCAGAACTGGCCTCT AACAGCCTGAGAGCCGAGGACACGGCTGTGTATTA

n in CACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA

o `z.
CGACTACTGGGGCCAGGGAACCCTGGTCACCGTGTC
cp o n.) PI TAGT
(SEQ ID NO: 909) (SEQ ID NO: 910) o oe 'a oe cA
oe

69 EIVMTQSPATLSVSPGERATLSCRASQSVDVNLAWYQ QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMHW
QKPGQAPRLLIYNAATRATGIPARVSGSGSGTEFTLTIS VRQAPGEGLEWVAAIWFDASDKYYADAVKGRFTISR
AA SLQSEDFAVYYCQQYQNWPLTFGGGTKVEIK

YWGQGTLVTVSS
n.) o (SEQ ID NO: 911) (SEQ ID NO: 912) oe GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGT
c,.) --.1 GTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGG CCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGC
o --.1 GCCAGTCAGAGTGTTCATACGAACTTAGCCTGGTAC ATCTGGATTCACCTTCAGTAACTATGGCATGCACTG
CAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATC GGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTGGG
TACAACGCAGCCACCAGGGCCACTGGTATCCCAGCC TGGCAGCTATATGGTTTGATGCAAGTGATAAATACT
AGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCACT ATGCAGACGCCGTGAAGGGCCGATTCACCATCTCCA
NA
CTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGCA GAGACAACTCCAAGAACACGCTGTATCTGCAAATG
GTTTATTACTGTCAGCAGTATCAGAACTGGCCTCTC AACAGCCTGAGAGCCGAGGACACGGCTGTGTATTA
ACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA
CTGTGCGAGAGATATTGCGATTTTTGGAGTGGTCCC
CGACTACTGGGGCCAGGGAACCCTGGTCACCGTGTC
TAGT
p (SEQ ID NO: 913) (SEQ ID NO: 914) .
L.
EIVMTQSPATLSVSPGERATLSCRASQSVHTNLAWYQ QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMHW
"
, o QKPGQAPRLLIYNAATRATGIPARFSGSGSGTEFTLTIS VRQAPGEGLEWVAAIWFDASDKYYADAVKGRFTISR
.
.7r N, n o AA SLQSEDFAVYYCQQYQNWPLTFGGGTKVEIK
DNSKNTLYLQMNSLRAEDTAVYYCARDIAIFGVVPDY
PI WGQGTLVTVSS
(SEQ ID NO: 915) (SEQ ID NO: 916) , L.
, GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGT
GTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGG CCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGC
GCCAGTCAGAGTGTTAACCTGAACTTAGCCTGGTAC ATCTGGATTCACCTTCAGTAACTATGGCATGCACTG
CAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATC GGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTGGG
TACCAGGCAGCCACCAGGGCCACTGGTATCCCAGCC TGGCAGCTATATGGTTTGATGCAAGTGATAAATACT
AGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCACT ATGCAGACGCCGTGAAGGGCCGATTCACCATCTCCA
NA
CTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGCA GAGACAACTCCAAGAACACGCTGTATCTGCAAATG
GTTTATTACTGTCAGCAGTATAACCAGTGGCCTCTC AACAGCCTGAGAGCCGAGGACACGGCTGTGTATTA

n .7r ACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA CTGTGCGAGAGATTTGGCGATTTTTGGAGTGGTCCC

f 9) fl CGACTACTGGGGCCAGGGAACCCTGGTCACCGTGTC
cp o n.) PI TAGT
(SEQ ID NO: 917) (SEQ ID NO: 918) o oe 'a oe cA
oe EIVMTQ SP ATL SVSPGERATL SCRASQSVNLNLAWYQ QVQLVE SGGGVVQPGRSLRL
SCAASGFTFSNYGMHW
QKP GQAPRLLIYQAATRATGIPARF S GS GS GTEFTLTI S VRQAP GE GLEWVAAIWFD
ASDKYYADAVKGRFTI SR
AA SLQSEDFAVYYCQQYNQWPLTFGGGTKVEIK

YWGQGTLVTVSS
n.) o (SEQ ID NO: 919) (SEQ ID NO: 920) oe i-J
GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGT
c,.) --.1 GTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGG CCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGC
o --.1 GCCAGTCAGAGTGTTTTCCAGAACTTAGCCTGGTAC ATCTGGATTCACCTTCAGTAACTATGGCATGCACTG
CAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATC GGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTGGG
TACCAGGCAGCCACCAGGGCCACTGGTATCCCAGCC TGGCAGCTATATGGTTTGATGCAAGTGATAAATACT
AGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCACT ATGCAGACGCCGTGAAGGGCCGATTCACCATCTCCA
NA
CTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGCA GAGACAACTCCAAGAACACGCTGTATCTGCAAATG
GTTTATTACTGTCAGCAGTATAACCAGTGGCCTCTC AACAGCCTGAGAGCCGAGGACACGGCTGTGTATTA
ACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA
CTGTGCGAGAGATATTGCGATTTTTGGAGTGGTCCC
CGACTACTGGGGCCAGGGAACCCTGGTCACCGTGTC
TAGT
p (SEQ ID NO: 921) (SEQ ID NO: 922) .
L.
EIVMTQ SPATL SVSPGERATL SCRASQSVFQNLAWYQ QVQLVE SGGGVVQPGRSLRL
SCAASGFTFSNYGMHW "
, o, QKP GQAPRLLIYQAATRATGIPARF S GS GS GTEFTLTI S VRQAP GE GLEWVAAIWFD
ASDKYYADAVKGRFTI SR .
f el o AA SLQSEDFAVYYCQQYNQWPLTFGGGTKVEIK
DNSKNTLYLQMNSLRAEDTAVYYCARDIAIFGVVPDY
PI WGQGTLVTVSS
(SEQ ID NO: 923) (SEQ ID NO: 924) , L.
, GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGT
GTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGG CCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGC
GCCAGTCAGAGTGTTGATAGACACTTAGCCTGGTAC ATCTGGATTCACCTTCCAGAACTATGGCATGCACTG
CAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATC GGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTGGG
TACGAAGCAGCCACCAGGGCCACTGGTATCCCAGC TGGCAGCTATATGGTTTGATGCGTACGGTAAATACT
CAGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCAC ATGCAGACGCCGTGAAGGGCCGATTCACCATCTCCA
NA
TCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGC GAGACAACTCCAAGAACACGCTGTATCTGCAAATG
AGTTTATTACTGTCAGCAGTATAACCAGTGGCCTCT AACAGCCTGAGAGCCGAGGACACGGCTGTGTATTA

n N CACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA

o fl CGACTACTGGGGCCAGGGAACCCTGGTCACCGTGTC
cp o n.) PI TAGT
(SEQ ID NO: 925) (SEQ ID NO: 926) o oe 'a oe cA
oe EIVMTQ SP ATL SV SP GERATL SCRASQ SVDRHLAWYQ QVQLVESGGGVVQPGRSLRL
SCAASGFTFQNYGMHW
QKP GQAPRLLIYEAATRATGIPARF S GS GS GTEFTLTI S VRQAP GE GLEWVAAIWFD
AYGKYYADAVKGRFTI SR
AA SLQSEDFAVYYCQQYNQWPLTFGGGTKVEIK

YWGQGTLVTVSS
n.) o (SEQ ID NO: 927) (SEQ ID NO: 928) oe i-J
GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGT
c,.) --.1 GTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGG CCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGC
o --.1 GCCAGTCAGAGTGTTGATAGACACTTAGCCTGGTAC ATCTGGATTCACCTTCCAGAACTATGGCATGCACTG
CAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATC GGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTGGG
TACGAAGCAGCCACCAGGGCCACTGGTATCCCAGC TGGCAGCTATATGGTTTGATGCGTACGGTAAATACT
CAGGGTCAGTGGCAGTGGGTCTGGGACAGAGTTCA ATGCAGACGCCGTGAAGGGCCGATTCACCATCTCCA
NA
CTCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTG GAGACAACTCCAAGAACACGCTGTATCTGCAAATG
CAGTTTATTACTGTCAGCAGTATAACCAGTGGCCTC AACAGCCTGAGAGCCGAGGACACGGCTGTGTATTA
TCACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA CTGTGCGAGAGATCAGACGATTTTTGGAGTGGTCCC
CGACTACTGGGGCCAGGGAACCCTGGTCACCGTGTC
TAGT
p (SEQ ID NO: 929) (SEQ ID NO: 930) .
L.
EIVMTQ SP ATL SV SP GERATL SCRASQ SVDRHLAWYQ
QVQLVESGGGVVQPGRSLRLSCAASGFTFQNYGMHW "
, N QKP GQAPRLLIYEAATRATGIPARVS GS GS GTEFTLTI S VRQAP GE GLEWVAAIWFD
AYGKYYADAVKGRFTI SR .
o N, AA SLQSEDFAVYYCQQYNQWPLTFGGGTKVEIK
DNSKNTLYLQMNSLRAEDTAVYYCARDQTIFGVVPD
PI YWGQGTLVTVSS
(SEQ ID NO: 931) (SEQ ID NO: 932) , L.
, GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGT
GTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGG CCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGC
GCCAGTCAGAGTGTTAACCGGCACTTAGCCTGGTAC ATCTGGATTCACCTTCCAGAACTATGGCATGCACTG
CAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATC GGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTGGG
TACGAAGCAGCCACCAGGGCCACTGGTATCCCAGC TGGCAGCTATATGGTTTGATGCGTACGGTAAATACT
CAGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCAC ATGCAGACGCCGTGAAGGGCCGATTCACCATCTCCA
NA
TCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGC GAGACAACTCCAAGAACACGCTGTATCTGCAAATG
AGTTTATTACTGTCAGCAGTATAACCAGTGGCCTCT AACAGCCTGAGAGCCGAGGACACGGCTGTGTATTA

n ,- CACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA

n CGACTACTGGGGCCAGGGAACCCTGGTCACCGTGTC
cp o n.) PI TAGT
(SEQ ID NO: 933) (SEQ ID NO: 934) o oe 'a oe cA
oe EIVMTQ SP ATL SV SP GERATL SCRASQ SVNRHLAWYQ QVQLVESGGGVVQPGRSLRL
SCAASGFTFQNYGMHW
QKP GQAPRLLIYEAATRATGIPARF S GS GS GTEFTLTI S VRQAP GE GLEWVAAIWFD
AYGKYYADAVKGRFTI SR
AA SLQSEDFAVYYCQQYNQWPLTFGGGTKVEIK

YWGQGTLVTVSS
n.) o (SEQ ID NO: 935) (SEQ ID NO: 936) oe i-J
GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGT
c,.) --.1 GTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGG CCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGC
o --.1 GCCAGTCAGAGTGTTGAAAGACACTTAGCCTGGTAC ATCTGGATTCACCTTCCAGAACTATGGCATGCACTG
CAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATC GGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTGGG
TACGAAGCAGCCACCAGGGCCACTGGTATCCCAGC TGGCAGCTATATGGTTTGATGCGTACGGTAAATACT
CAGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCAC ATGCAGACGCCGTGAAGGGCCGATTCACCATCTCCA
NA
TCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGC GAGACAACTCCAAGAACACGCTGTATCTGCAAATG
AGTTTATTACTGTCAGCAGTATCAGCAGTGGCCTCT AACAGCCTGAGAGCCGAGGACACGGCTGTGTATTA
CACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA CTGTGCGAGAGATAAGACGATTTTTGGAGTGGTCCC
CGACTACTGGGGCCAGGGAACCCTGGTCACCGTGTC
TAGT
p (SEQ ID NO: 937) (SEQ ID NO: 938) .
L.
EIVMTQ SP ATL SV SPGERATL SCRASQ SVERHLAWYQ QVQLVESGGGVVQPGRSLRL
SCAASGFTFQNYGMHW "
, QKP GQAPRLLIYEAATRATGIPARF S GS GS GTEFTLTI S VRQAP GE GLEWVAAIWFD
AYGKYYADAVKGRFTI SR .
.7r N, n o AA SLQSEDFAVYYCQQYQQWPLTFGGGTKVEIK
DNSKNTLYLQMNSLRAEDTAVYYCARDKTIFGVVPD
PI YWGQGTLVTVSS
(SEQ ID NO: 939) (SEQ ID NO: 940) , L.
, GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGT
GTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGG CCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGC
GCCAGTCAGAGTGTTTTCAGACACTTAGCCTGGTAC ATCTGGATTCACCTTCAGTAACTATGGCATGCACTG
CAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATC GGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTGGG
TACGAAGCAGCCACCAGGGCCACTGGTATCCCAGC TGGCAGCTATATGGTTTGATGCGTACGGTAAATACT
CAGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCAC ATGCAGACGCCGTGAAGGGCCGATTCACCATCTCCA
NA
TCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGC GAGACAACTCCAAGAACACGCTGTATCTGCAAATG
AGTTTATTACTGTCAGCAGTATCAGAACTGGCCTCT AACAGCCTGAGAGCCGAGGACACGGCTGTGTATTA

n c, CACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA

,-n CGACTACTGGGGCCAGGGAACCCTGGTCACCGTGTC
cp o n.) PI TAGT
(SEQ ID NO: 941) (SEQ ID NO: 942) o oe 'a oe cA
oe EIVMTQ SP ATL SVSP GERATL SCRASQ SVFRHLAWYQ QVQLVE SGGGVVQPGRSLRL
SCAASGFTFSNYGMHW
QKP GQAPRLLIYEAATRATGIPARF S GS GS GTEFTLTI S VRQAP GE GLEWVAAIWFD
AYGKYYADAVKGRFTI SR
AA SLQSEDFAVYYCQQYQNWPLTFGGGTKVEIK

YWGQGTLVTVSS
n.) o (SEQ ID NO: 943) (SEQ ID NO: 944) oe i-J
GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGT
c,.) --.1 GTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGG CCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGC
o --.1 GCCAGTCAGAGTGTTCTGAGTCACTTAGCCTGGTAC ATCTGGATTCACCTTCCAGAACTATGGCATGCACTG
CAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATC GGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTGGG
TACGAAGCAGCCACCAGGGCCACTGGTATCCCAGC TGGCAGCTATATGGTTTGATGCGTACGACAAATACT
CAGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCAC ATGCAGACGCCGTGAAGGGCCGATTCACCATCTCCA
NA
TCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGC GAGACAACTCCAAGAACACGCTGTATCTGCAAATG
AGTTTATTACTGTCAGCAGTATAACAACTGGCCTCT AACAGCCTGAGAGCCGAGGACACGGCTGTGTATTA
CACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA CTGTGCGAGAGATAAGTCGATTTTTGGAGTGGTCCC
CGACTACTGGGGCCAGGGAACCCTGGTCACCGTGTC
TAGT
p (SEQ ID NO: 945) (SEQ ID NO: 946) .
L.
EIVMTQ SP ATL SV SP GERATL SCRASQ SVL SHLAWYQ QVQLVESGGGVVQPGRSLRL
SCAASGFTFQNYGMHW "
, QKP GQAPRLLIYEAATRATGIPARF S GS GS GTEFTLTI S VRQAP GE GLEWVAAIWFD
AYDKYYADAVKGRFTI SR .
(I o AA SLQSEDFAVYYCQQYNNWPLTFGGGTKVEIK
DNSKNTLYLQMNSLRAEDTAVYYCARDKSIFGVVPD
PI YWGQGTLVTVSS
(SEQ ID NO: 947) (SEQ ID NO: 948) , L.
, GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGT
GTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGG CCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGC
GCCAGTCAGAGTGTTAACAGACACTTAGCCTGGTAC ATCTGGATTCACCTTCCAGAACTATGGCATGCACTG
CAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATC GGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTGGG
TACGAAGCAGCCACCAGGGCCACTGGTATCCCAGC TGGCAGCTATATGGTTTGATGCGTACGACAAATACT
CAGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCAC ATGCAGACGCCGTGAAGGGCCGATTCACCATCTCCA
NA
TCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGC GAGACAACTCCAAGAACACGCTGTATCTGCAAATG
AGTTTATTACTGTCAGCAGTATAACAACTGGCCTCT AACAGCCTGAGAGCCGAGGACACGGCTGTGTATTA

n in CACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA

.7r n CGACTACTGGGGCCAGGGAACCCTGGTCACCGTGTC
cp o n.) PI TAGT
(SEQ ID NO: 949) (SEQ ID NO: 950) o oe 'a oe cA
oe EIVMTQ SP ATL SV SP GERATL SCRASQ SVNRHLAWYQ QVQLVESGGGVVQPGRSLRL
SCAASGFTFQNYGMHW
QKP GQAPRLLIYEAATRATGIPARF S GS GS GTEFTLTI S VRQAP GE GLEWVAAIWFD
AYDKYYADAVKGRFTI SR
AA SLQSEDFAVYYCQQYNNWPLTFGGGTKVEIK

YWGQGTLVTVSS
n.) o (SEQ ID NO: 951) (SEQ ID NO: 952) oe i-J
GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGT
c,.) --.1 GTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGG CCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGC
o --.1 GCCAGTCAGAGTGTTACCAGCCACTTAGCCTGGTAC ATCTGGATTCACCTTCCAGAACTATGGCATGCACTG
CAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATC GGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTGGG
TACGAAGCAGCCACCAGGGCCACTGGTATCCCAGC TGGCAGCTATATGGTTTGATGCGTACGACAAATACT
CAGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCAC ATGCAGACGCCGTGAAGGGCCGATTCACCATCTCCA
NA
TCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGC GAGACAACTCCAAGAACACGCTGTATCTGCAAATG
AGTTTATTACTGTCAGCAGTATAACCAGTGGCCTCT AACAGCCTGAGAGCCGAGGACACGGCTGTGTATTA
CACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA CTGTGCGAGAGATCTCGCGATTTTTGGAGTGGTCCC
CGACTACTGGGGCCAGGGAACCCTGGTCACCGTGTC
TAGT
p (SEQ ID NO: 953) (SEQ ID NO: 954) .
L.
EIVMTQ SP ATL SV SP GERATL SCRASQ SVT SHLAWYQ QVQLVESGGGVVQPGRSLRL
SCAASGFTFQNYGMHW "
, in QKP GQAPRLLIYEAATRATGIPARF S GS GS GTEFTLTI S VRQAP GE GLEWVAAIWFD
AYDKYYADAVKGRFTI SR .
f el o AA SLQSEDFAVYYCQQYNQWPLTFGGGTKVEIK
DNSKNTLYLQMNSLRAEDTAVYYCARDLAIFGVVPD
PI YWGQGTLVTVSS
(SEQ ID NO: 955) (SEQ ID NO: 956) , L.
, GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGT
GTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGG CCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGC
GCCAGTCAGAGTGTTGATCAGCACTTAGCCTGGTAC ATCTGGATTCACCTTCCAGAACTATGGCATGCACTG
CAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATC GGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTGGG
TACCAGGCAGCCACCAGGGCCACTGGTATCCCAGCC TGGCAGCTATATGGTTTGATGCGGCTTTCAAATACT
AGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCACT ATGCAGACGCCGTGAAGGGCCGATTCACCATCTCCA
NA
CTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGCA GAGACAACTCCAAGAACACGCTGTATCTGCAAATG
GTTTATTACTGTCAGCAGTATCAGAACTGGCCTCTC AACAGCCTGAGAGCCGAGGACACGGCTGTGTATTA

n o ACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA

f e) f el CGACTACTGGGGCCAGGGAACCCTGGTCACCGTGTC
cp o n.) PI TAGT
(SEQ ID NO: 957) (SEQ ID NO: 958) o oe 'a oe cA
oe EIVMTQSPATLSVSPGERATLSCRASQSVDQHLAWYQ QVQLVESGGGVVQPGRSLRLSCAASGFTFQNYGMHW
QKPGQAPRLLIYQAATRATGIPARFSGSGSGTEFTLTIS VRQAPGEGLEWVAAIWFDAAFKYYADAVKGRFTISR
AA SLQSEDFAVYYCQQYQNWPLTFGGGTKVEIK

YWGQGTLVTVSS
n.) o (SEQ ID NO: 959) (SEQ ID NO: 960) oe i-J
ATGGACATGAGGGTGCCCGCTCAGCTCCTGGGGCTC ATGGACATGAGGGTGCCCGCTCAGCTCCTGGGGCTC
c,.) --.1 CTGCTGCTGTGGCTGAGAGGTGCGCGCTGTGAAATC CTGCTGCTGTGGCTGAGAGGTGCGCGCTGTCAGGTG
o --.1 GTGATGACGCAGTCTCCAGCCACCCTGTCTGTGTCT CAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
CCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAG TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGG
TCAGAGTGTTAGCGAACACTTAGCCTGGTACCAGCA ATTCACCTTCAGTAACTATGGCATGCACTGGGTCCG
GAAACCTGGCCAGGCTCCCAGGCTCCTCATCTACGA CCAGGCTCCAGGCGAGGGGCTGGAGTGGGTGGCAG
NA
,- AGCAGCCACCAGGGCCACTGGTATCCCAGCCAGGTT
CTATCTGGTTTGATGCAAGTGATAAATACTATGCAG
oe re) CAGTGGCAGTGGGTCTGGGACAGAGTTCACTCTCAC
ACGCCGTGAAGGGCCGATTCACCATCTCCAGAGAC
o, " CATCAGCAGCCTGCAGTCTGAAGATTTTGCAGTT AACTCCAAGAACACGCTGTATCTGCAAATGAACAG
in ci3 CCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGC
0.0 ¨ GAGA
p (SEQ ID NO: 1377 (SEQ ID NO: 1378 .
L.
EIVMTQSPATLSVSPGERATLSCRASQSVSEHLAWYQ QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMHW
.
, QKPGQAPRLLIYEAATRATGIPARFSGSGSGTEFTLTIS VRQAPGEGLEWVAAIWFDASDKYYADAVKGRFTISR
.
AA SLQSEDFAVYYCQQYQNWPLTFGGGTKVEIK
DNSKNTLYLQMNSLRAEDTAVYYCARDLAIFGVIPDY o , WGQGTLVTVSS
, (SEQ ID NO: 1086) (SEQ ID NO: 1287) ' L.
, ATGGACATGAGGGTGCCCGCTCAGCTCCTGGGGCTC ATGGACATGAGGGTGCCCGCTCAGCTCCTGGGGCTC
CTGCTGCTGTGGCTGAGAGGTGCGCGCTGTGAAATC CTGCTGCTGTGGCTGAGAGGTGCGCGCTGTCAGGTG
GTGATGACGCAGTCTCCAGCCACCCTGTCTGTGTCT CAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
CCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAG TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGG
TCAGAGTGTTAGCAGCAACTTAGCCTGGTACCAGCA ATTCACCTTCAGTAACTATGGCATGCACTGGGTCCG
c-1 oe A GAAACCTGGCCAGGCTCCCAGGCTCCTCATCTATGG CCAGGCTCCAGGCGAGGGGCTGGAGTGGGTGGCAG

rn N
o, TGCAGCCACCAGGGCCACTGGTATCCCAGCCAGGTT
CTATCTGGTTTGATGCAAGTGATAAATACTATGCAG
"
in CAGTGGCAGTGGGTCTGGGACAGAGTTCACTCTCAC
ACGCCGTGAAGGGCCGATTCACCATCTCCAGAGAC oo cz n 0.0 CATCAGCAGCCTGCAGTCTGAAGATTTTGCAGTT AACTCCAAGAACACGCTGTATCTGCAAATGAACAG

¨
CCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGC
cp GAGA
n.) o (SEQ ID NO: 1379 (SEQ ID NO: 1380 oe 'a AA
EIVMTQSPATLSVSPGERATLSCRASQSVSSNLAWYQQ QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMHW
w oe KPGQAPRLLIYGAATRATGIPARFSGSGSGTEFTLTISS VRQAPGEGLEWVAAIWFDASDKYYADAVKGRFTISR
cA
oe LQSEDFAVYYCQQYNNWPLTFGGGTKVEIK
DNSKNTLYLQMNSLRAEDTAVYYCARDIAIFGVVPDY
WGQGTLVTVSS
(SEQ ID NO: 1296) (SEQ ID NO: 1297) n.) ATGGACATGAGGGTGCCCGCTCAGCTCCTGGGGCTC ATGGACATGAGGGTGCCCGCTCAGCTCCTGGGGCTC
=
CTGCTGCTGTGGCTGAGAGGTGCGCGCTGTGAAATC CTGCTGCTGTGGCTGAGAGGTGCGCGCTGTCAGGTG
oe i-J
GTGCTGACGCAGTCTCCAGCCACCCTGTCTCTGTCT CAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
c,.) --.1 CCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAG TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGG
o o --.1 TCAGAGTGTTAGCAGCAACTTAGCCTGGTACCAGCA ATTCACCTTCAGTAACTATGGCATGCACTGGGTCCG
NA GAAACCTGGCCAGGCTCCCAGGCTCCTCATCTATGG CCAGGCTCCAGGCGAGGGGCTGGAGTGGGTGGCAG
N TGCAGCCACCAGGGCCACTGGTATCCCAGACAGGTT
CTATCTGGTTTGATGCAAGTGATAAATACTATGCAG
o rn CAGTGGCAGTGGGTCTGGGACAGAGTTCACTCTCAC
ACGCCGTGAAGGGCCGATTCACCATCTCCAGAGAC
o r'l CATCAGCAGGCTGGAGCCTGAAGATTTTGCAGTT AACTCCAAGAACACGCTGTATCTGCAAATGAACAG
in ci3 CCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGC
0.0 ¨ GAGA
(SEQ ID NO: 1381 (SEQ ID NO: 1382 EIVLTQSPATLSLSPGERATLSCRASQSVSSNLAWYQQ QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMHW
p AA KPGQAPRLLIYGAATRATGIPDRFSGSGSGTEFTLTISR
VRQAPGEGLEWVAAIWFDASDKYYADAVKGRFTISR .
L.
LEPEDFAVYYCQQYNNWPLTFGGGTKVEIK
DNSKNTLYLQMNSLRAEDTAVYYCARDQAIFGVVPD .
, YWGQGTLVTVSS
.
(SEQ ID NO: 1306) (SEQ ID NO: 1307) , ATGGACATGAGGGTGCCCGCTCAGCTCCTGGGGCTC ATGGACATGAGGGTGCCCGCTCAGCTCCTGGGGCTC
, CTGCTGCTGTGGCTGAGAGGTGCGCGCTGTGAAATC CTGCTGCTGTGGCTGAGAGGTGCGCGCTGTCAGGTG
' L.
, GTGCTGACGCAGTCTCCAGCCACCCTGTCTCTGTCT CAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
CCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAG TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGG
TCAGAGTGTTAGCGAACACTTAGCCTGGTACCAGCA ATTCACCTTCAGTAACTATGGCATGCACTGGGTCCG
GAAACCTGGCCAGGCTCCCAGGCTCCTCATCTACGA CCAGGCTCCAGGCGAGGGGCTGGAGTGGGTGGCAG
o NA
o AGCAGCCACCAGGGCCACTGGTATCCCAGACAGGT CTATCTGGTTTGATGCAAGTGATAAATACTATGCAG
re) ACGCCGTGAAGGGCCGATTCACCATCTCCAGAGAC
"
in CCATCAGCAGGCTGGAGCCTGAAGATTTTGCAGTT
AACTCCAAGAACACGCTGTATCTGCAAATGAACAG
ci3 0.0 CCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGC oo -n GAGA

(SEQ ID NO: 1383 (SEQ ID NO: 1384 cp EIVLTQSPATLSLSPGERATLSCRASQSVSEHLAWYQQ QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMHW
n.) o AA
KPGQAPRLLIYEAATRATGIPDRFSGSGSGTEFTLTISR VRQAPGEGLEWVAAIWFDASDKYYADAVKGRFTISR
oe 'a LEPEDFAVYYCQQYQNWPLTFGGGTKVEIK
DNSKNTLYLQMNSLRAEDTAVYYCARDLAIFGVIPDY c,.) oe WGQGTLVTVSS
o oe (SEQ ID NO: 1316) (SEQ ID NO: 1317) ATGGACATGAGGGTGCCCGCTCAGCTCCTGGGGCTC ATGGACATGAGGGTGCCCGCTCAGCTCCTGGGGCTC
CTGCTGCTGTGGCTGAGAGGTGCGCGCTGTGAAATC CTGCTGCTGTGGCTGAGAGGTGCGCGCTGTCAGGTG

n.) GTGCTGACGCAGTCTCCAGCCACCCTGTCTCTGTCT CAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
=
CCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAG TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGG
oe i-J
TCAGAGTGTTAGCAGCAACTTAGCCTGGTACCAGCA ATTCACCTTCAGTAACTATGGCATGCACTGGGTCCG
c,.) --.1 GAAACCTGGCCAGGCTCCCAGGCTCCTCATCTATGG CCAGGCTCCAGGCGAGGGGCTGGAGTGGGTGGCAG
o o NA
--.1 o TGCAGCCACCAGGGCCACTGGTATCCCAGACAGGTT CTATCTGGTTTGATGCAAGTGATAAATACTATGCAG

o .7r CAGTGGCAGTGGGTCTGGGACAGAGTTCACTCTCAC
ACGCCGTGAAGGGCCGATTCACCATCTCCAGAGAC
o e'l CATCAGCAGGCTGGAGCCTGAAGATTTTGCAGTT AACTCCAAGAACACGCTGTATCTGCAAATGAACAG
in ci3 CCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGC
0.0 ¨ GAGA
(SEQ ID NO: 1385 (SEQ ID NO: 1386 EIVLTQSPATLSLSPGERATLSCRASQSVSSNLAWYQQ QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMHW
KPGQAPRLLIYGAATRATGIPDRFSGSGSGTEFTLTISR VRQAPGEGLEWVAAIWFDASDKYYADAVKGRFTISR
AA LEPEDFAVYYCQQYNNWPLTFGGGTKVEIK
DNSKNTLYLQMNSLRAEDTAVYYCARDIAIFGVVPDY p WGQGTLVTVSS
(SEQ ID NO: 1326) (SEQ ID NO: 1327) .
, ATGGACATGAGGGTGCCCGCTCAGCTCCTGGGGCTC ATGGACATGAGGGTGCCCGCTCAGCTCCTGGGGCTC
.
CTGCTGCTGTGGCTGAGAGGTGCGCGCTGTGAAATC CTGCTGCTGTGGCTGAGAGGTGCGCGCTGTCAGGTG
o , GTGCTGACGCAGTCTCCAGCCACCCTGTCTCTGTCT CAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
.
, , CCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAG TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGG
' L.
, TCAGAGTGTTGATCTGCACTTAGCCTGGTACCAGCA ATTCACCTTCAGTAACTATGGCATGCACTGGGTCCG
GAAACCTGGCCAGGCTCCCAGGCTCCTCATCTACGA CCAGGCTCCAGGCGAGGGGCTGGAGTGGGTGGCAG
NA
f9) AGCAGCCACCAGGGCCACTGGTATCCCAGACAGGT
CTATCTGGTTTGATGCAAGTGATAAATACTATGCAG
o .7r TCAGTGGCAGTGGGTCTGGGACAGAGTTCACTCTCA
ACGCCGTGAAGGGCCGATTCACCATCTCCAGAGAC
ff) r,1 CCATCAGCAGGCTGGAGCCTGAAGATTTTGCAGTT
AACTCCAAGAACACGCTGTATCTGCAAATGAACAG
in ci3 CCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGC
0.0 GAGA
¨
(SEQ ID NO: 1387 (SEQ ID NO: 1388 n EIVLTQSPATLSLSPGERATLSCRASQSVDLHLAWYQQ QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMHW

KPGQAPRLLIYEAATRATGIPDRFSGSGSGTEFTLTISR VRQAPGEGLEWVAAIWFDASDKYYADAVKGRFTISR
cp AA LEPEDFAVYYCQQYQNWPLTFGGGTKVEIK
DNSKNTLYLQMNSLRAEDTAVYYCARDLAIFGVVPD n.) o YWGQGTLVTVSS
oe 'a (SEQ ID NO: 1336) (SEQ ID NO: 1337) c,.) oe o oe CTGCTGCTGTGGCTGAGAGGTGCGCGCTGTGAAATC CTGCTGCTGTGGCTGAGAGGTGCGCGCTGTCAGGTG
GTGCTGACGCAGTCTCCAGCCACCCTGTCTCTGTCT CAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
CCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAG TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGG

n.) TCAGAGTGTTAACCTGAACTTAGCCTGGTACCAGCA ATTCACCTTCAGTAACTATGGCATGCACTGGGTCCG
o GAAACCTGGCCAGGCTCCCAGGCTCCTCATCTACCA CCAGGCTCCAGGCGAGGGGCTGGAGTGGGTGGCAG
oe i-J
GGCAGCCACCAGGGCCACTGGTATCCCAGACAGGT CTATCTGGTTTGATGCAAGTGATAAATACTATGCAG
c,.) --.1 TCAGTGGCAGTGGGTCTGGGACAGAGTTCACTCTCA ACGCCGTGAAGGGCCGATTCACCATCTCCAGAGAC
o o CCATCAGCAGGCTGGAGCCTGAAGATTTTGCAGTT AACTCCAAGAACACGCTGTATCTGCAAATGAACAG
--.1 CCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGC
GAGA
(SEQ ID NO: 1389 (SEQ ID NO: 1390 EIVLTQ SP ATL SL SP GERATL SCRASQ SVNLNLAWYQQ QVQLVE SGGGVVQPGRSLRL
SCAASGFTFSNYGMHW
KPGQAPRLLIYQAATRATGIPDRFSGSGSGTEFTLTISR VRQAPGEGLEWVAAIWFDASDKYYADAVKGRFTISR
AA LEPEDFAVYYCQQYNQWPLTFGGGTKVEIK
DNSKNTLYLQMNSLRAEDTAVYYCARDLAIFGVVPD
YWGQGTLVTVSS
(SEQ ID NO: 1346) (SEQ ID NO: 1347) p ATGGACATGAGGGTGCCCGCTCAGCTCCTGGGGCTC ATGGACATGAGGGTGCCCGCTCAGCTCCTGGGGCTC
.
L.
CTGCTGCTGTGGCTGAGAGGTGCGCGCTGTGAAATC CTGCTGCTGTGGCTGAGAGGTGCGCGCTGTCAGGTG
.
, GTGCTGACGCAGTCTCCAGCCACCCTGTCTCTGTCT CAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
.
CCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAG TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGG
, TCAGAGTGTTTTCAGCCACTTAGCCTGGTACCAGCA ATTCACCTTCCAGAACTATGGCATGCACTGGGTCCG
.
, , GAAACCTGGCCAGGCTCCCAGGCTCCTCATCTACGA CCAGGCTCCAGGCGAGGGGCTGGAGTGGGTGGCAG
.
, NA
L.
, in AGCAGCCACCAGGGCCACTGGTATCCCAGACAGGT
CTATCTGGTTTGATGCGTCTGACAAATACTATGCAG
o .7r TCAGTGGCAGTGGGTCTGGGACAGAGTTCACTCTCA
ACGCCGTGAAGGGCCGATTCACCATCTCCAGAGAC
o r'l CCATCAGCAGGCTGGAGCCTGAAGATTTTGCAGTT
AACTCCAAGAACACGCTGTATCTGCAAATGAACAG
in ci3 CCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGC
0.0 ¨ GAGA
(SEQ ID NO: 1391 (SEQ ID NO: 1392 EIVLTQ SP ATL SL SP GERATL SCRAS Q SVF SHLAWYQQ QVQLVESGGGVVQPGRSLRL
SCAASGFTFQNYGMHW
KPGQAPRLLIYEAATRATGIPDRFSGSGSGTEFTLTISR VRQAPGEGLEWVAAIWFDASDKYYADAVKGRFTISR

n AA LEPEDFAVYYCQQYQNWPLTFGGGTKVEIK

YWGQGTLVTVSS
cp (SEQ ID NO: 1356) (SEQ ID NO: 1357) n.) o oe 'a oe cA
oe Table 4. Exemplary CDRL1, CDRL2, CDRL3, CDRH1, CDRH2, and CDRH3 Nucleic Acid ("NA") and Amino Acid ("AA") Sequences w Table 4A. Exemplary CDRL1, CDRL2, and CDRL3 Nucleic Acid ('NA") and Amino Acid ("AA") Sequences o 1-, oe i-J
W
=TylWomoniiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiCpnriiiiiiiiiiiiiiiiiiiiiiiiiii iiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiii iiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiicowiii ii!i!i!i!i!i!i!i!i!i!Mg2Qommini!i!i!i!i!i!i!i!i!i!i!i!i!i!i!i!i!iiicOn3iniiiiii iiiiiiiiiiiiiiiiiiiimmga -4 =
AGGGCCAGTCAGAGTGTTGATAG GAAGCAGCCACCAGGGCCACT .CAGCAGTATCAGAACTGGCCTCT
o rn NA ACACTTAGCC CACT
o ,P1 (SEQ ID NO: 1) (SEQ ID NO: 2) (SEQ ID
NO: 3) o RASQSVDRHLA EAATRAT QQYQNWPLT
(SEQ ID NO: 4) (SEQ ID NO: 5) (SEQ ID
NO: 6) AGGGCCAGTCAGAGTGTTAACAG GAAGCAGCCACCAGGGCCACT CAGCAGTATCAGAACTGGCCTCT
71. NA ACACTTAGCC CACT
o ,P1 (SEQ ID NO: 7) (SEQ ID NO: 8) (SEQ ID
NO: 9) o P
RASQSVNRHLA EAATRAT QQYQNWPLT
(SEQ ID NO: 10) (SEQ ID NO: 11) (SEQ ID
NO: 12) .
AGGGCCAGTCAGAGTGTTCATAG GAAGCAGCCACCAGGGCCACT CAGCAGTATCAGAACTGGCCTCT
, rn NA ACACTTAGCC CACT
c, (-1 , ri (SEQ ID NO: 13) (SEQ ID NO: 14) (SEQ ID
NO: 15) ' , o , RASQSVHRHLA EAATRAT QQYQNWPLT
c, , , (SEQ ID NO: 16) (SEQ ID NO: 17) (SEQ ID
NO: 18) AGGGCCAGTCAGAGTGTTGAAAG GAAGCAGCCACCAGGGCCACT CAGCAGTATCAGAACTGGCCTCT
o NA
ACACTTAGCC CACT
o ,P1 (SEQ ID NO: 19) (SEQ ID NO: 20) (SEQ ID
NO: 21) o RASQSVERHLA EAATRAT QQYQNWPLT
c:ji AA
(SEQ ID NO: 22) (SEQ ID NO: 23) (SEQ ID
NO: 24) AGGGCCAGTCAGAGTGTTTTCAG GAAGCAGCCACCAGGGCCACT CAGCAGTATCAGAACTGGCCTCT
1-d NA ACACTTAGCC CACT
n ,-i ,-, ,P1 (SEQ ID NO: 25) (SEQ ID NO: 26) (SEQ ID
NO: 27) o cp RASQSVFRHLA EAATRAT QQYQNWPLT
w o (SEQ ID NO: 28) (SEQ ID NO: 29) (SEQ ID
NO: 30) oe 'a oe o oe oo (.9) x r, IWO
339VII3VaD
o VN
oo IDIDOODIOVVDVDIVIDVaDVD IDVDaDODVDDVDaDVaDVVD
DVDIaLIDIDVDVDIDVDaDODV
,-= (99 :ON CH OHS) (S9 :ON CH OHS) (179 :ON CH OHS) el VV
ci) rIcIMNOAO0 IVIIIVVH VIHSINASOSVII
P
(E9 :ON CH OHS) (Z9 :ON CH OHS) (19 :ON CH OHS) c,.) Pi IWO
3aDVII3V3L VN w IDIDOODIOVVDVDIVIDVaDVD IDVDaDODVDDVDaDVaDVVD DVDIVIIDIDVDVDIDVDaDODV
(09 :ON CH OHS) (6g :ON CH OHS) (8S :cm m Os) rIcIMNOAO0 IVIIIVVH VIHSIASOSVII o (LS :ON CFI OHS) (9g :ON CH OHS) (SS :cm m Os) 44 k.) IWO DaDVII3VaL
VN 4==
IDIDOODIOVVDVDIVIDVaDVD IDVDaDODVDDVDaDVaDVVD DVDIaLIDIDVDVDIDVDaDODV
, (17g :ON CFI OHS) (Eg :ON CFI OHS) (ZS :ON m Os) , . vv '' , , rIcIANNAO0 IVIIIVVH VIHSIASOSVII
, o ' QS :ON CFI OHS) (Og :ON CFI OHS) (617 :ON CEI OHS) 44 .:, IWO DaDVII3VaL
VN oe , ' .
IDIDOODIOVVOVVIVIDVaDVD IDVDaDODVDDVDaDVaDVVD
DVDIaLIDIDVDVDIDVDaDODV
o (817 :ON CFI OHS) (L17 :ON CFI OHS) (917 :ON CH OHS) VV
rIcIMNOAO0 IVIIIVVH VIHIMASOSVII
P
(St :ON CFI OHS) (1717 :ON CFI OHS) (Et :ON m Os) c:

VN w IDIDOODIOVVDVDIVIDVaDVD IDVDaDODVDDVDaDVaDVVD OVIVOLLDIDVDVDIDVDaDODV
(Z17 :ON CFI OHS) (117 :ON CFI OHS) (017 :ON m Os) rIcIMNOAO0 IVIIIVVH VII-IIIHASOSVII
P
(6E :ON CH OHS) (8E :ON CFI OHS) (LE :ON m Os) c:
N IWO

o, o N
IDIDOODIOVVDVDIVIDVaDVD IDVDaDODVDDVDaDVaDVVD
OVVVOLLDIDVDVDIDVDaDODV
(.9) el (9E :ON CH OHS) (SE :ON CFI OHS) (17E :cm m Os) oe vv '' ,. rIcIMNOAO0 IVIIIVVH VIHIINASOSVII
o el o 0 (EE :ON CFI OHS) (ZE :ON CFI OHS) (I E :ON m Os) =c,,, c:

IDIDOODIOVVDVDIVIDVaDVD IDVDaDODVDDVDaDVaDVVD OVOVVIIDIDVDVDIDVDaDODV
13d-OM-179T Z-V

oo (.9) oe rIcIMNOAO0 IVIIIVVH VIHSAASOSVII VV r.) o oo (SOT :ON CFI OHS) (170I :ON CFI OHS) (E0I :ON m OHs) Z), =
el IWO
DaDVIIDVDD VN o, o ci) IDIDOODIOVVDVDIVIDVaDVD IDVDaDODVDDVDaDVaDVVD 9V3LLLL9I9V9V3L9V3aD99V
E*- (ZOI :ON CFI OHS) (TOT :ON CFI OHS) (00i :ON m OHs) Pi rIcIMNOAO0 IVIIIVVH VIHSAASOSVII
P
(66 :ON CH OHS) (86 :ON CH OHS) (L6 :ON (II OHS) c,.) o IWO DaDVIIDVDD
VN ' IDIDOODIOVVDVDIVIDVaDVD IDVDaDODVDDVDaDVaDVVD 9V3LLLL9I9V9V3L9V3aD99V
(II :ON CFI OHS) (g6 :ON CH OHS) (176 :ON CH OHS) VV k6 rIdMI-10A00 IVIIIVVH VII-IIISASOSVII
P
(E6 :ON CH OHS) (Z6 :ON CH OHS) (16 :ON CH OHS) c,.) , IWO
33-DVLIDVD-D VN w , , IaLDaDDIDVaDVDIVIDVaDVD I3VDaD99V33V3aDVaDVV9 93aDVII9I9V9V319V3aD99V
, (06 :ON CH OHS) (68 :ON CH OHS) (88 :ON m Os) 1JdA1NOAO0 IVIIIVVH VII-IHSASOSVII
, ' . (L8 :ON CFI OHS) (98 :ON CH OHS) (g8 :om m Os) L
k.) o IWO 339V1I3V3V VN
IDIDOODIOVV-DVDIVIDVaDVD I3VDaD99V33V3aDVaDVV9 V9aDVII9I9V9V319V3aD99V
(78 :ON CFI OHS) (8 :ON CFI OHS) (Z8 :om m Os) 1JdA1NOAO0 IVIIIVVH VII-IHSASOSVII
P
(I8 :ON CFI OHS) (08 :ON CFI OHS) (6L :ON CH OHS) c,.) r.) VN =
IDIDOODIOVV-DVDIVIDVaDVD I3VDaD99V33V3aDVaDVV9 V9aDVII9I9V9V319V3aD99V
(8L :ON CFI OHS) (LL :ON CFI OHS) (9L :ON CH OHS) VV k6 N 1JdA1NOAO0 IVIIIVVH VIITICEASOSVII
o, P
t--= (SL :ON CFI OHS) (17L :ON CFI OHS) (EL :ON m Os) w " IWO
33-DV1I3VD-D VN ' oo ,-IDIDOODIOVV-DVDIVIDVaDVD I3V30099V33V300VaDVV9 o el 0 (ZL :ON CFI OHS) (IL :ON CFI OHS) (OL :om m Os) vv 1JdA1NOAO0 IVIIIVVH VII-IrIASOSVII
(69 :ON CH OHS) (89 :ON CH OHS) (L9 :ON CH OHS) 13d-0M-179T Z-V

oo (.9) oo (.9) o oo (17171 :ON CFI WS) (EtT :ON CFI OHS) (Z171 :ON m Os) ,.
VV kt4 = rIcIANNAO0 IVITIVVH VIHIAASOSVIT
el 5:
ci) (ItT :ON CFI WS) (0171 :ON CFI OHS) (6E1 :ON CH OHS) c,.) E*- IWO
33-DVII3VaD VN c:
c.) Pi IDIDOODIOVVOVVIVIDVaDVD I3VDaD99V33V3aDVaDVV9 OVOILLIDIDVDVaLDVDaDODV
(SET :ON CFI WS) (LET :ON CFI OHS) (9ET :ON CH
OHS) VV k6 rIcIMOOAO0 IVITIVVH VII-ISSASOSVIT
5:
(SET :ON CFI WS) (17T :ON CFI OHS) (EET :ON m Os) c,.) 4==
IWO DaDVIIDVDD
VN 4.
IDIDOODIDVaDVDIVIDVaDVD I3VDaD99V33V3aDVaDVV9 9VI9VII9I9V9V3L9V3aD99V
(ZET :ON CFI OHS) 0E1 :ON CFI OHS) WET :ON m OHs) , vv '' , ridAVNIOAO0 IVITIVVH VIHSOASOSVIT
. o , , (6ZI :ON CH WS) (SZT :ON CFI OHS) (LZT :ON m Os) , IWO DaDVIIDVDD VN
.:, IDIDOODIOVV-DVDIVIDVaDVD I3VDaD99V33V3aDVaDVV9 9V9V3LL9I9V9V3L9V3aD99V
, ' . (9ZT :ON CH WS) (SZT :ON CFI OHS) (17ZI :ON m Os) vv '' rIcIMOOAO0 IVITIVVH VIHSAASOSVIT

5:
(EZT :ON CFI OHS) (ZZI :ON CFI OHS) (I Z1 :ON m OHs) c:
IWO DaDVIIDVDD
VN oe IDIDOODIDVaDVDIVIDVaDVD I3VDaD99V33V3aDVaDVV9 OVOILLIDIDVDVaLDVDaDODV
(OZT :ON CFI OHS) (611 :ON CEI OHS) (SIT :ON m OHs) VV kt4 rIcIMOOAO0 IVITIVVH VIHSAASOSVIT
5:
(LIT :ON CFI OHS) (911 :ON CEI OHS) (SIT :ON m OHs) c,.) c:
IWO DaDVIIDVDD
VN co N
IDIDOODIDVaDVDIVIDVaDVD I3VDaD99V33V3aDVaDVV9 OVOILLIDIDVDVaLDVDaDODV
o, N= (17T 1 :ON CFI OHS) (ET 1 :ON CFI OHS) (z1 1 :ON m OHs) m VV k6) el rIcIMOOAO0 IVITIVVH VIHSIASOSVIT
oo o ,- (I 1 1 :ON CFI OHS) (OTT :ON CFI OHS) (60T :ON CEI OHS) 44 or.) el 3aDVII3V3L VN
IDIDOODIDVaDVDIVIDVaDVD I3VDaD99V33V3aDVaDVV9 9V9I3LI9I9V9V3L9V3aD99V
(80T :ON CFI OHS) (LOT :ON CFI OHS) (901 :ON CEI OHS) 13d-OM-179T Z-V

AGGGCCAGTCAGAGTGTTTTCAC GAAGCAGCCACCAGGGCCACT CAGCAGTATAACAACTGGCCTCT
o NA
GCACTTAGCC CACT
`z. (SEQ ID NO: 145) (SEQ ID NO: 146) (SEQ ID
NO: 147) o n.) RASQSVFTHLA EAATRAT QQYNNWPLT
o PI AA
oe (SEQ ID NO: 148) (SEQ ID NO: 149) (SEQ ID
NO: 150) t''J
AGGGCCAGTCAGAGTGTTTTTGA GAAGCAGCCACCAGGGCCACT CAGCAGTATAACAACTGGCCTCT
--.1 o (-,1 NA ACACTTAGCC CACT
--.1 ,--i ri (SEQ ID NO: 151) (SEQ ID NO: 152) (SEQ ID
NO: 153) o ,-I RASQSVFEHLA EAATRAT QQYNNWPLT
(SEQ ID NO: 154) (SEQ ID NO: 155) (SEQ ID
NO: 156) AGGGCCAGTCAGAGTGTTGAACA GAAGCAGCCACCAGGGCCACT CAGCAGTATAACAACTGGCCTCT
cr NA GCACTTAGCC CACT
ri (SEQ ID NO: 157) (SEQ ID NO: 158) (SEQ ID
NO: 159) o RASQSVEQHLA EAATRAT QQYNNWPLT
PI AA
P
(SEQ ID NO: 160) (SEQ ID NO: 161) (SEQ ID
NO: 162) .
L.
AGGGCCAGTCAGAGTGTTCATAG GAAGCAGCCACCAGGGCCACT CAGCAGTATAACCAGTGGCCTCT
.
N NA CCACTTAGCC CACT
, (.91 (SEQ ID NO: 163) (SEQ ID NO: 164) (SEQ ID
NO: 165) " o , RASQSVHSHLA EAATRAT QQYNQWPLT
.
, PI AA
, ' (SEQ ID NO: 166) (SEQ ID
NO: 167) (SEQ ID NO: 168) L.
, AGGGCCAGTCAGAGTGTTCATCA GAAGCAGCCACCAGGGCCACT CAGCAGTATAACCAGTGGCCTCT
oe NA TCACTTAGCC CACT
rn n (SEQ ID NO: 169) (SEQ ID NO: 170) (SEQ ID
NO: 171) o RASQSVHHHLA EAATRAT QQYNQWPLT
PI AA
(SEQ ID NO: 172) (SEQ ID NO: 173) (SEQ ID
NO: 174) AGGGCCAGTCAGAGTGTTCATAG GAAGCAGCCACCAGGGCCACT CAGCAGTATAACAACTGGCCTCT
7r NA CCACTTAGCC CACT

,-, n ri (SEQ ID NO: 175) (SEQ ID NO: 176) (SEQ ID
NO: 177) 1-3 o RASQSVHSHLA EAATRAT QQYNNWPLT
PI AA
cp n.) (SEQ ID NO: 178) (SEQ ID NO: 179) (SEQ ID
NO: 180) =
AGGGCCAGTCAGAGTGTTGATGT GAAGCAGCCACCAGGGCCACT CAGCAGTATAACCAGTGGCCTCT
oe C., NA
CAACTTAGCC CACT
'a oe cA
oe (SEQ ID NO: 181) (SEQ ID NO: 182) (SEQ ID
NO: 183) RASQSVDVNLA EAATRAT QQYNQWPLT
AA

(SEQ ID NO: 184) (SEQ ID NO: 185) (SEQ ID
NO: 186) n.) AGGGCCAGTCAGAGTGTTGATGT GAAGCAGCCACCAGGGCCACT CAGCAGTATAACCAGTGGCCTCT
o 1-, oe ,--1 NA CCACTTAGCC CACT
t''J
ri (SEQ ID NO: 187) (SEQ ID NO: 188) (SEQ ID
NO: 189) -4 o o v:, ,-I RASQSVDVHLA EAATRAT QQYNQWPLT

(SEQ ID NO: 190) (SEQ ID NO: 191) (SEQ ID
NO: 192) AGGGCCAGTCAGAGTGTTTTTGA GAAGCAGCCACCAGGGCCACT CAGCAGTATAACAACTGGCCTCT
NA ACACTTAGCC CACT
o ri (SEQ ID NO: 193) (SEQ ID NO: 194) (SEQ ID
NO: 195) o ,-I RASQSVFEHLA EAATRAT QQYNNWPLT
(SEQ ID NO: 196) (SEQ ID NO: 197) (SEQ ID
NO: 198) AGGGCCAGTCAGAGTGTTTTTGA GAAGCAGCCACCAGGGCCACT CAGCAGTATAACAACTGGCCTCT
NA ACACTTAGCC CACT
P
`z. (SEQ ID NO: 199) (SEQ ID NO: 200) (SEQ ID
NO: 201) .
RASQSVFEHLA EAATRAT QQYNNWPLT
, ,0 PI AA
.
(SEQ ID NO: 202) (SEQ ID NO: 203) (SEQ ID
NO: 204) , AGGGCCAGTCAGAGTGTTTTCGA GAAGCAGCCACCAGGGCCACT CAGCAGTATAACCAGTGGCCTCT
.
, , in NA ACACTTAGCC CACT
, ri (SEQ ID NO: 205) (SEQ ID NO: 206) (SEQ ID
NO: 207) o ,-I RASQSVFEHLA EAATRAT QQYNQWPLT
(SEQ ID NO: 208) (SEQ ID NO: 209) (SEQ ID
NO: 210) AGGGCCAGTCAGAGTGTTCTGGA GAAGCAGCCACCAGGGCCACT CAGCAGTATAACAACTGGCCTCT
rn NA ACACTTAGCC CACT
.7r ri (SEQ ID NO: 211) (SEQ ID NO: 212) (SEQ ID
NO: 213) o ,-I RASQSVLEHLA EAATRAT QQYNNWPLT
Iv (SEQ ID NO: 214) (SEQ ID NO: 215) (SEQ ID
NO: 216) 1-3 rn AGGGCCAGTCAGAGTGTTGATAG GAAGCAGCCACCAGGGCCACT
CAGCAGTATAACCAGTGGCCTCT
cp (T1 NA ACACTTAGCC CACT
o o 1-, (SEQ ID NO: 217) (SEQ ID NO: 218) (SEQ ID NO: 219) oe 'a " AA RASQSVDRHLA EAATRAT QQYNQWPLT
c,.) oe cr oe oo (e) oo (e) o oo (8SZ :ON CFI WS) (LSZ :ON CFI OHS) (9SZ :ON CH OHS) ,-VV kt4 = IldANNAO0 el P
ci) (SSZ :ON CFI WS) (17SZ :ON CFI OHS) (ESZ :ON m Os) c,.) 4==
E*- IWO

c.) Pi IDIDaDDIOVVIVVIVIDVaDVD IDVOYDDDVDDVOYDVaDIDD
DVaDVIIDIDVDVDIDVOYDODV
(ZSZ :ON CFI OHS) (I SZ :ON CFI OHS) (OSZ :ON m OHs) ridANNA66 IvInvvo VINSSASOSVII
P
(617Z :ON CH WS) (817Z :ON CFI OHS) (L17Z :ON m Os) c,.) 4==

IDIDaDDIOVVIVVIVIDVaDVD IDVOYDDDVDDVOYDVaDIDD DVaDVIIDIDVDVDIDVOYDODV
(917Z :ON CH WS) (g17Z :ON CFI OHS) (1717Z :ON m Os) , vv '' , rIcIMNOAO0 IVIIIVVH VII-LLIASOSVII
. o , ' (El :ON (11 WS) (Z17Z :ON (11 OHS) (I 17Z :ON aj Os) =c,,, , c:
IWO DODVIIDVDD
VN c`
.:, IDIDOODIOVVDVDIVIDVaDVD I3VOYD99V33V3YDVaDVV9 DVDIaLIDIDVDVDIDVOYDODV
, ' . (017Z :ON CH WS) (6EZ :ON CH OHS) (8EZ :ON m Os) vv '' rIcIMNOAO0 IVIIIVVH VII-LLIASOSVII

P
(LEZ :ON (11 WS) (9EZ :ON al OHS) (SEZ :ON m Os) c,.) c:
IWO DODVIIDVDD
VN c`
IDIDOODIOVVDVDIVIDVaDVD I3VOYD99V33V3YDVaDVV9 DVDIaLIDIDVDVDIDVOYDODV
(tEZ :ON (11 WS) (EEZ :ON (11 OHS) (ZEZ :ON aj Os) VV kt4 IldMONAO0 IVITIVVO VIHANASOSVII
P
(TEZ :ON CFI OHS) (0EZ :ON CFI OHS) (6ZZ :ON (II OHS) c,.) IWO DODVIIDVDV VN
N
IDIDOODIDVDOVVIVIDVaDVD IDVOYDODVDDVOYDVaDDVD
IDOVVIIDIDVDVDIDVOYDODV
o N= (8ZZ :ON CFI WS) (LZZ :ON CFI OHS) (9ZZ :ON CH OHS) el rIcIMOOAO0 IVIIIVVH VIHIINASOSVII
oo o ,- (SZZ :ON CH WS) (17ZZ :ON CH OHS) (EZZ :ON aj Os) =
.
el o IDIDOODIDVaDVDIVIDVaDVD I3VOYD99V33V3YDVaDVV9 DOOVVIIDIDVDVDIDVOYDODV
(ZZZ :ON CH WS) (I ZZ :ON CFI OHS) (OZZ :ON aj OHS) 13d-OM-179T Z-V

oo r.) x r) IWO
DaDVIIOVVO
o VN
oo IDIDOODIDVDOVVIVIOVaDVD IDVOYDOOVDDVDaDVaDOVO
IDOVVIIDIOVOVOIOVOYDOOV
,-= (176Z :ON CH OHS) (6Z :ON CH OHS) (Z6Z :ON CH OHS) ci) rldA1NOAO0 IVIIIVVN VINIHASOSVII P
(I6Z :ON CH OHS) (06Z :ON CH OHS) (68Z :ON CH OHS) w Pi IWO DaDVIIOVVO VN c:
IDIDOODIOVVOVOIVIOVaDVD IDVOYDOOVDDVDDOVaDOVV OVIVaLIDIOVOVOIOVOYDOOV
(88Z :ON m Os) (Lsz :cm m Os) (98z :cm CH OHS) rldA1NOAO0 IVIIIVVN VINACEASOSVII o (g8Z :ON m Os) (tsz :om m Os) (Esz :ON m Os) =c,,, c:

IDIDOODIOVVOVOIVIOVaDVD IDVOYDOOVDDVDDOVaDOVV IDIVOLLOIOVOVOIOVOYDOOV
, (Z8Z :ON m Os) (I sz :om m Os) (osz :om ajOHs) , . vv '' , , ridAVNIOA66 IVIIIVVN VINACEASOSVII
, o ' (6LZ :ON CH OHS) (8LZ :cm m Os) (LLz :cm m Os) 44 c:

VN 'A
, ' .
IDIDOODIOVVOVOIVIOVaDVD IDVOYDOOVDDVDDOVaDOVV
IDIVOLLOIOVOVOIOVOYDOOV
o (9LZ :ON CH OHS) (SLZ :cm m Os) (i7Lz :cm m Os) rIcIANNAO0 IVIIIVVH VINSSASOSVII P
(ELZ :cm m Os) (az :cm m Os) (iLz :cm m Os) 4=.

IDIDaDDIOVVIVVIVIOVaDVD IDVOYDOOVDDVDaDVaDVVO OVaDVIIDIOVOVOIOVOYDOOV
(OLZ :ON m Os) (69z :cm CH OHS) (89Z :ON CH
OHS) VV k6 rldANNAO0 IVIIIVV9 VINSSASOSVII P
(L9Z :ON CH WS) (99Z :ON CH OHS) (g9Z :ON CH OHS) cl=
4=.
N IWO

o o N
IDIDaDDIOVVIVVIVIOVaDVD IDVOYDOOVDDVDaDVaDIDO
OVaDVIIDIOVOVOIOVOYDOOV
r.) el (I79Z :ON CH OHS) (9Z :ON CH OHS) (Z9Z :ON CH OHS) ,- rldANNAO0 o el o 0 (NZ :ON CH OHS) (09Z :ON CH OHS) (6SZ :ON CH OHS) 44 4=.

VN c`
IDIDaDDIOVVIVVIVIOVaDVD IDVOYDOOVDDVDaDVaDIDO OVaDVIIDIOVOVOIOVOYDOOV
13d-OM-179T Z-V

oo (.9) (.9) rIcIMNOAO0 IVITIVVH VIT-TITAASOSVIT VV r.) o oo (EEE :ON CFI OHS) (ZEE :ON CFI OHS) (TEE :ON m OHs) Z), =
el IWO
33-DVLI3V3V VN c,.) ci) IDIDOODIOVV-DVDIVIDVaDVD I3VDaD99V33V3aDVaDVV9 OVOILLIDIDVDVaLDVDaDODV
(OEE :ON CFI WS) (6ZE :ON CH OHS) (8ZE :ON m Os) Pi rIcIMOOAO0 IVITIVVH VIT-TITHASOSVIT
P
(LZE :ON CFI WS) (9ZE :ON CH OHS) (SZE :ON m Os) c,.) 4=.

VN w IDIDOODIDVaDVDIVIDVaDVD I3VDaD99V33V3aDVaDVV9 9VVV9LL9I9V9V3L9V3aD99V
(I7ZE :ON m Os) (EzE :ON m Os) (zzE :ON m Os) rIcIMONAO0 IVITIVVH VIT-IIINASOSVIT
P
Oa :ON CFI OHS) (Oa :ON CFI OHS) (6T E :ON CH OHS) c,.) , r.) , IWO
33-DVLIDVD-D VN ' , , IDIDaDDIDVDOVVIVIDVaDVD I3VDaD99V33V3aDVaDVV9 933VVII9I9V9V3L9V3aD99V
, (8I E :ON CFI OHS) (LIE :ON CFI OHS) (9TE :ON CH OHS) rIcIMONAO0 IVITIVVH VIT-IIICEASOSVIT
, ' . (SI E :ON CFI OHS) (17T E :ON CFI OHS) (ET E :ON m OHs) *c., c:

IDIDaDDIDVDOVVIVIDVaDVD I3VDaD99V33V3aDVaDVV9 9VIV9LL9I9V9V3L9V3aD99V
(ZI E :ON CFI OHS) (I I E :ON CFI OHS) (0 I E :ON m OHs) rIcIMONAO0 IVITIVVH VIT-IIICEASOSVIT
P
(60 :ON CET WS) (80E :ON m Os) (LoE :ON m Os) c,.) c:

IDIDaDDIDVDOVVIVIDVaDVD I3VDaD99V33V3aDVaDVV9 9VIV9LL9I9V9V3L9V3aD99V
(90E :ON CET WS) (SOE :ON m Os) (toE :ON m Os) N riamONA66 ivxivv6 vlmOdAsOsvx c, P
t--= (OE :ON m Os) (zoE :ON m Os) (TOE :ON m Os) w " IWO
DaDVLL3VV9 VN
oo ,- IDIDOODIDVDOVVIVIDVaDVD IDVDaDODVDDVDaDVaDDVD
V33ILLI9I9V9V3L9V3aD99V
o el 0 (00E :ON m Os) (66z :ON CET OHS) (86Z :ON CET OHS) VV
rIdMONAOO IVITIVVO VININASOSVIT
(L6Z :ON CET WS) (96Z :ON CET OHS) (S6Z :ON CET OHS) 13d-OM-179T Z-V

oo r.) oo r.) o (ET
:ON CFI OHS) QM :ON CFI OHS) (OM :ON CFI OHS) x NAT 00176ZS:Sd!
¨1 o rldANNAO0 IVIIIVV9 VINSSASOSVII
el ci) (ET :ON CFI OHS) QM
:ON CH OHS) (OZEI :ON CFI OHS) NAT
66E6ZS:Sd!
rldA1NOAO0 IVIIIVVH VII-THSASOSVII
c.) Pi (ZI ET :ON CFI OHS) (I
1E1 :ON CFI OHS) ((NET :ON CFI OHS) NAT
L6E6ZS:Sd!
rldANNAO0 IVIIIVV9 VINSSASOSVII
(ZOEI :ON CFI OHS) (IOU :ON CFI OHS) (00EI :ON CFI OHS) NAT
Z8E6ZS:Sd!
rldANNAO0 IVIIIVV9 VINSSASOSVII
(Z6ZI :ON CH OHS) (I 6ZI :ON CH OHS) (06Z1 :ON CH OHS) VV
I8E6ZS:Sd!
rldA1NOAO0 IVIIIVVH VII-THSASOSVII
(09E :ON CH OHS) (6SE :ON CH OHS) (8SE :ON m Os) VV k6) en IldMNOAO0 IVNIVVO VIHOCRSOSVII

o 0 I
a, (Lc E :ON CH OHS) (9SE :ON CH OHS) (SSE :ON m Os) w IWO DODVIIDVDD
VN c:
.:, IDIDOODIOVVDVDIVIDVaDVD IDVOYDODVDDVOYDVaDDVD VaLVDIIDIDVDVDIDVOYDODV
, ' (17SE :ON CFI OHS) (ESE :ON CFI OHS) (ZSE :ON m Os) ,n vv '"
rIcIMONAO0 IVIIIVVH VIHSIASOSVII

P
(ISE :ON CFI OHS) (OSE :ON CFI OHS) (617E :ON (II OHS) w w IWO DaDVIIDVDD
VN u'l IDIDaDDIDVDOVVIVIDVaDVD I3VOYD99V33V3YDVaDVV9 DVDDVIIDIDVDVDIDVOYDODV
(817E :ON CFI OHS) (Lt E :ON CFI OHS) (917E :ON
CH OHS) VV kt4 rIcIANNAO0 IVIIIVVH VII-IIINASOSVII P
(g17 :ON CFI OHS) (1717 :ON CFI OHS) (17 :ON m Os) w 4==
IWO DODVIIDVDV
VN u4 N
IDIDOODIOVVOVVIVIDVaDVD I3VOYD99V33V3YDVaDVV9 DVOVVIIDIDVDVDIDVOYDODV
o, = N (Z17E :ON CH O(Ti HS) (T :ON CFI OHS) (017E :ON m OHs) el rIcIANNAO0 IVIIIVVH VIHSIASOSVII
oo o ¨1 (6EE :ON CH OHS) (SEE :ON CFI OHS) (LEE :ON m Os) =
w el o IWO 3aDVII3V3L VN w IDIDOODIOVVOVVIVIDVaDVD I3VOYD99V33V3YDVaDVV9 DVDIaLIDIDVDVDIDVOYDODV
(9EE :ON CH OHS) (SEE :ON CH OHS) (17EE :ON aj Ws) 13d-OM-179T Z-V

oo (.9) oo (.9) oo ci) E=1 en en en en 0,1 (WET :ON CH OHS) (19ET :ON CH OHS) (09E-1 :ON CH OHS) VV
S0176ZS: Sol!
dA1N6A66 IVITIVVH VIHSAASOSVIT
oo (ZSEI :ON CFI OHS) (I SET :ON CFI OHS) (OSET :ON CFI OHS) el=
VV 170176ZS:S=1!
rldMONAOO IVITIVVO VININASOSVIT
(ZtET :ON CFI OHS) (TtET :ON CFI OHS) (017ET :ON CFI OHS) VV
0176ZS:Sd!
rldMNOAO0 IVITIVVH VIHICEASOSVIT
13d-0M-179T Z-V

t..) Table 4B. Exemplary CDRH1, CDRH2, and CDRH3 Nucleotide and Amino Acid Sequences o ,-, oe i-J
QiAbiiiiii iiiiiiiiIA).0 COMM1111112p!i!i!i!i!i!i!i!i!i!i!i!i!i!i!i!i!i!i!i!i!i!i!i!i!i!i!i!i!iiiicpRini iiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiii iiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiicMpiiiiiiiiiiiii iiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiniiiiiiii -4 =
AACTATGGCATGCAC GCTATATGGTTTGATGCAAGTGA
GATTTGGCGATTTTTGGAGTGGT o TAAATACTATGCAGACGCCGTGA CCCCGACTAC
NA
rn AGGGC
o 'I (SEQ ID NO: 361) (SEQ ID NO: 362) (SEQ ID
NO: 363) NYGMH AIWFDASDKYYADAVKG
DLAIFGVVPDY
C:4 AA
(SEQ ID NO: 364) (SEQ ID NO: 365) (SEQ ID
NO: 366) AACTATGGCATGCAC GCTATATGGTTTGATGCAAGTGA
GATTTGGCGATTTTTGGAGTGGT
TAAATACTATGCAGACGCCGTGA CCCCGACTAC
NA
.71. AGGGC
P
o 'I (SEQ ID NO: 367) (SEQ ID NO: 368) (SEQ ID
NO: 369) o .
NYGMH AIWFDASDKYYADAVKG
DLAIFGVVPDY .
r., PI AA
, (SEQ ID NO: 370) (SEQ ID NO: 371) (SEQ ID
NO: 372) .
r., AACTATGGCATGCAC GCTATATGGTTTGATGCAAGTGA
GATTTGGCGATTTTTGGAGTGGT .
, , TAAATACTATGCAGACGCCGTGA CCCCGACTAC
, NA
, rn AGGGC
(-1 , 'I (SEQ ID NO: 373) (SEQ ID NO: 374) (SEQ ID
NO: 375) NYGMH AIWFDASDKYYADAVKG
DLAIFGVVPDY
C:4 AA
(SEQ ID NO: 376) (SEQ ID NO: 377) (SEQ ID
NO: 378) AACTATGGCATGCAC GCTATATGGTTTGATGCAAGTGA
GATTTGGCGATTTTTGGAGTGGT
TAAATACTATGCAGACGCCGTGA CCCCGACTAC
NA
o AGGGC
o 'I (SEQ ID NO: 379) (SEQ ID NO: 380) (SEQ ID
NO: 381) Iv c:, n NYGMH AIWFDASDKYYADAVKG
DLAIFGVVPDY
C:4 AA

(SEQ ID NO: 382) (SEQ ID NO: 383) (SEQ ID
NO: 384) cp AACTATGGCATGCAC GCTATATGGTTTGATGCAAGTGA
GATTTGGCGATTTTTGGAGTGGT n.) ,--i o fl TAAATACTATGCAGACGCCGTGA CCCCGACTAC
oe =
NA 'a AGGGC
c,.) t^1 (SEQ ID NO: 385) (SEQ ID NO: 386) (SEQ ID
NO: 387) oe o oe NYGMH AIWFDASDKYYADAVKG
DLAIFGVVPDY
AA
(SEQ ID NO: 388) (SEQ ID NO: 389) (SEQ ID
NO: 390) AACTATGGCATGCAC GCTATATGGTTTGATGCAAGTGA

n.) TAAATACTATGCAGACGCCGTGA CCCCGACTAC
o NA
oe .7r AGGGC
`z. (SEQ ID NO: 391) (SEQ ID NO: 392) (SEQ ID
NO: 393) -4 =
o NYGMH AIWFDASDKYYADAVKG
DLAIFGVVPDY o AA

(SEQ ID NO: 394) (SEQ ID NO: 395) (SEQ ID
NO: 396) AACTATGGCATGCAC GCTATATGGTTTGATGCAAGTGA
GATTTGGCGATTTTTGGAGTGGT
TAAATACTATGCAGACGCCGTGA CCCCGACTAC
NA
o AGGGC
=
`z. (SEQ ID NO: 397) (SEQ ID NO: 398) (SEQ ID
NO: 399) =
NYGMH AIWFDASDKYYADAVKG
DLAIFGVVPDY

(SEQ ID NO: 400) (SEQ ID NO: 401) (SEQ ID
NO: 402) AACTATGGCATGCAC GCTATATGGTTTGATGCAAGTGA
GATTTGGCGATTTTTGGAGTGGT p TAAATACTATGCAGACGCCGTGA CCCCGACTAC
NA .
re) AGGGC
.
=
, `z. (SEQ ID NO: 403) (SEQ ID NO: 404) (SEQ ID
NO: 405) ..
NYGMH AIWFDASDKYYADAVKG
DLAIFGVVPDY
PI AA
, ,0 (SEQ ID NO: 406) (SEQ ID NO: 407) (SEQ ID
NO: 408) , , , AACTATGGCATGCAC GCTATATGGTTTGATGCAAGTGA
GATTTGGCGATTTTTGGAGTGGT
, TAAATACTATGCAGACGCCGTGA CCCCGACTAC
NA
co AGGGC
,--i fl (SEQ ID NO: 409) (SEQ ID NO: 410) (SEQ ID
NO: 411) NYGMH AIWFDASDKYYADAVKG
DLAIFGVVPDY
=,,i AA
(SEQ ID NO: 412) (SEQ ID NO: 413) (SEQ ID
NO: 414) AACTATGGCATGCAC GCTATATGGTTTGATGCAAGTGA
GATTTGGCGATTTTTGGAGTGGT
TAAATACTATGCAGACGCCGTGA CCCCGACTAC

NA
n .7r AGGGC

fl (SEQ ID NO: 415) (SEQ ID NO: 416) (SEQ ID
NO: 417) =
cp NYGMH AIWFDASDKYYADAVKG
DLAIFGVVPDY w o (SEQ ID NO: 418) (SEQ ID NO: 419) (SEQ ID
NO: 420) oe 'a oe cr oe AACTATGGCATGCAC GCTATATGGTTTGATGCAAGTGA
GATTTGGCGATTTTTGGAGTGGT
NA TAAATACTATGCAGACGCCGTGA CCCCGACTAC
AGGGC

n (SEQ ID NO: 421) (SEQ ID NO: 422) (SEQ ID
NO: 423) o =
NYGMH AIWFDASDKYYADAVKG
DLAIFGVVPDY oe AA
i-J
(SEQ ID NO: 424) (SEQ ID NO: 425) (SEQ ID
NO: 426) c,.) o AACTATGGCATGCAC GCTATATGGTTTGATGCAAGTGA
GATTTGGCGATTTTTGGAGTGGT

TAAATACTATGCAGACGCCGTGA CCCCGACTAC
NA
in AGGGC
,--i n (SEQ ID NO: 427) (SEQ ID NO: 428) (SEQ ID
NO: 429) =
NYGMH AIWFDASDKYYADAVKG
DLAIFGVVPDY

(SEQ ID NO: 430) (SEQ ID NO: 431) (SEQ ID
NO: 432) AACTATGGCATGCAC GCTATATGGTTTGATGCAAGTGA
GATTTGGCGATTTTTGGAGTGGT
TAAATACTATGCAGACGCCGTGA CCCCGACTAC
NA
,--i AGGGC
re) P
n (SEQ ID NO: 433) (SEQ ID NO: 434) (SEQ ID
NO: 435) .

NYGMH AIWFDASDKYYADAVKG
DLAIFGVVPDY .
, (SEQ ID NO: 436) (SEQ ID NO: 437) (SEQ ID
NO: 438) ..' AACTATGGCATGCAC GCTATATGGTTTGATGCAAGTGA
GATCTGGCGATTTTTGGAGTGAT .
, TAAATACTATGCAGACGCCGTGA TCCCGACTAC
' , NA
o o AGGGC ' n (SEQ ID NO: 439) (SEQ ID NO: 440) (SEQ ID NO: 441) =
NYGMH AIWFDASDKYYADAVKG
DLAIFGVIPDY

(SEQ ID NO: 442) (SEQ ID NO: 443) (SEQ ID
NO: 444) AACTATGGCATGCAC GCTATATGGTTTGATGCAAGTGA
GATTTGGCGATTTTTGGAGTGGT
TAAATACTATGCAGACGCCGTGA CCCCGACTAC
NA
co AGGGC
fl (SEQ ID NO: 445) (SEQ ID NO: 446) (SEQ ID
NO: 447) NYGMH AIWFDASDKYYADAVKG
DLAIFGVVPDY n =,,i (SEQ ID NO: 448) (SEQ ID NO: 449) (SEQ ID
NO: 450) cp re) AACTATGGCATGCAC GCTATATGGTTTGATGCAAGTGA
GATTTGGCGATTTTTGGAGTGGT n.) o n TAAATACTATGCAGACGCCGTGA CCCCGACTAC
oe NA
'a C.7 AGGGC
c,.) (-1 r (SEQ ID NO: 451) (SEQ ID NO: 452) (SEQ ID
NO: 453) oe cr oe NYGMH AIWFDASDKYYADAVKG
DLAIFGVVPDY
AA
(SEQ ID NO: 454) (SEQ ID NO: 455) (SEQ ID
NO: 456) AACTATGGCATGCAC GCTATATGGTTTGATGCGTCTGA

n.) CAAATACTATGCAGACGCCGTGA CCCCGACTAC
o NA
oe ,--i AGGGC
n (SEQ ID NO: 457) (SEQ ID NO: 458) (SEQ ID
NO: 459) -4 =
o NYGMH AIWFDASDKYYADAVKG
DLAIFGVVPDY o AA

(SEQ ID NO: 460) (SEQ ID NO: 461) (SEQ ID
NO: 462) AACTATGGCATGCAC GCTATATGGTTTGATGCGTCTGA
GATCTTGCGATTTTTGGAGTGGT
CAAATACTATGCAGACGCCGTGA CCCCGACTAC
NA
,--i AGGGC
=
`z. (SEQ ID NO: 463) (SEQ ID NO: 464) (SEQ ID
NO: 465) =
NYGMH AIWFDASDKYYADAVKG
DLAIFGVVPDY

(SEQ ID NO: 466) (SEQ ID NO: 467) (SEQ ID
NO: 468) AACTATGGCATGCAC GCTATATGGTTTGATGCGTCTGA
GATCTTGCGATTTTTGGAGTGGT p CAAATACTATGCAGACGCCGTGA CCCCGACTAC
NA .
o AGGGC
.
n (SEQ ID NO: 469) (SEQ ID NO: 470) (SEQ ID
NO: 471) ..
NYGMH AIWFDASDKYYADAVKG
DLAIFGVVPDY
PI AA
, ,0 (SEQ ID NO: 472) (SEQ ID NO: 473) (SEQ ID
NO: 474) , , , AACTATGGCATGCAC GCTATATGGTTTGATGCAAGTGA
GATTTGGCGATTTTTGGAGTGGT
, TAAATACTATGCAGACGCCGTGA CCCCGACTAC
NA
co AGGGC
=
fl (SEQ ID NO: 475) (SEQ ID NO: 476) (SEQ ID
NO: 477) NYGMH AIWFDASDKYYADAVKG
DLAIFGVVPDY
=,,i AA
(SEQ ID NO: 478) (SEQ ID NO: 479) (SEQ ID
NO: 480) AACTATGGCATGCAC GCTATATGGTTTGATGCAAGTGA
GATTTGGCGATTTTTGGAGTGGT
TAAATACTATGCAGACGCCGTGA CCCCGACTAC

NA
n x AGGGC
=

`z. (SEQ ID NO: 481) (SEQ ID NO: 482) (SEQ ID
NO: 483) =
cp NYGMH AIWFDASDKYYADAVKG
DLAIFGVVPDY w o (SEQ ID NO: 484) (SEQ ID NO: 485) (SEQ ID
NO: 486) oe 'a oe cr oe AACTATGGCATGCAC GCTATATGGTTTGATGCAAGTGA
GATATTGCGATTTTTGGAGTGGT
NA TAAATACTATGCAGACGCCGTGA CCCCGACTAC
AGGGC

re) l=.) fl (SEQ ID NO: 487) (SEQ ID NO: 488) (SEQ ID
NO: 489) o =
NYGMH AIWFDASDKYYADAVKG
DIAIFGVVPDY oe AA
i-J
(SEQ ID NO: 490) (SEQ ID NO: 491) (SEQ ID
NO: 492) c,.) o AACTATGGCATGCAC GCTATATGGTTTGATGCAAGTGA
GATATTGCGATTTTTGGAGTGGT vo TAAATACTATGCAGACGCCGTGA CCCCGACTAC
NA
.7r AGGGC
.7r fl (SEQ ID NO: 493) (SEQ ID NO: 494) (SEQ ID
NO: 495) =
NYGMH AIWFDASDKYYADAVKG
DIAIFGVVPDY

(SEQ ID NO: 496) (SEQ ID NO: 497) (SEQ ID
NO: 498) AACTATGGCATGCAC GCTATATGGTTTGATGCAAGTGA
GATTTGGCGATTTTTGGAGTGGT
TAAATACTATGCAGACGCCGTGA CCCCGACTAC
NA
o AGGGC
fl (SEQ ID NO: 499) (SEQ ID NO: 500) (SEQ ID
NO: 501) .

NYGMH AIWFDASDKYYADAVKG
DLAIFGVVPDY .
, (SEQ ID NO: 502) (SEQ ID NO: 503) (SEQ ID
NO: 504) ..' AACTATGGCATGCAC GCTATATGGTTTGATGCAAGTGA
GATTTGGCGATTTTTGGAGTGGT .
, TAAATACTATGCAGACGCCGTGA CCCCGACTAC
' , NA
o o AGGGC ' `z.
(SEQ ID NO: 505) (SEQ ID NO: 506) (SEQ ID NO: 507) =
NYGMH AIWFDASDKYYADAVKG
DLAIFGVVPDY

(SEQ ID NO: 508) (SEQ ID NO: 509) (SEQ ID
NO: 510) AACTATGGCATGCAC GCTATATGGTTTGATGCAAGTGA
GATTTGGCGATTTTTGGAGTGGT
TAAATACTATGCAGACGCCGTGA CCCCGACTAC
NA
AGGGC
,--i fl (SEQ ID NO: 511) (SEQ ID NO: 512) (SEQ ID
NO: 513) NYGMH AIWFDASDKYYADAVKG
DLAIFGVVPDY n =,,i (SEQ ID NO: 514) (SEQ ID NO: 515) (SEQ ID
NO: 516) cp AACTATGGCATGCAC GCTATATGGTTTGATGCAAGTGA
GATTTGGCGATTTTTGGAGTGGT n.) o fl TAAATACTATGCAGACGCCGTGA CCCCGACTAC
oe NA
'a C.7 AGGGC
c,.) c4 o (SEQ ID NO: 517) (SEQ ID NO: 518) (SEQ ID
NO: 519) oe cr oe NYGMH AIWFDASDKYYADAVKG
DLAIFGVVPDY
AA
(SEQ ID NO: 520) (SEQ ID NO: 521) (SEQ ID
NO: 522) AACTATGGCATGCAC GCTATATGGTTTGATGCAAGTGA

n.) TAAATACTATGCAGACGCCGTGA CCCCGACTAC
o NA
oe N AGGGC
n (SEQ ID NO: 523) (SEQ ID NO: 524) (SEQ ID
NO: 525) -4 =
o NYGMH AIWFDASDKYYADAVKG
DLAIFGVVPDY o AA

(SEQ ID NO: 526) (SEQ ID NO: 527) (SEQ ID
NO: 528) AACTATGGCATGCAC GCTATATGGTTTGATGCAAGTGA
GATTTGGCGATTTTTGGAGTGGT
TAAATACTATGCAGACGCCGTGA CCCCGACTAC
NA
oe AGGGC
re) n (SEQ ID NO: 529) (SEQ ID NO: 530) (SEQ ID
NO: 531) =
NYGMH AIWFDASDKYYADAVKG
DLAIFGVVPDY

(SEQ ID NO: 532) (SEQ ID NO: 533) (SEQ ID
NO: 534) AACTATGGCATGCAC GCTATATGGTTTGATGCAAGTGA
GATTTGGCGATTTTTGGAGTGGT p TAAATACTATGCAGACGCCGTGA CCCCGACTAC
NA .
.7r AGGGC
.
n (SEQ ID NO: 535) (SEQ ID NO: 536) (SEQ ID
NO: 537) ..
NYGMH AIWFDASDKYYADAVKG
DLAIFGVVPDY
PI AA
, ,0 (SEQ ID NO: 538) (SEQ ID NO: 539) (SEQ ID
NO: 540) , , , AACTATGGCATGCAC GCTATATGGTTTGATGCAAGTGA
GATTTGGCGATTTTTGGAGTGGT
, TAAATACTATGCAGACGCCGTGA CCCCGACTAC
NA
N AGGGC
R (SEQ ID NO: 541) (SEQ ID NO: 542) (SEQ ID
NO: 543) NYGMH AIWFDASDKYYADAVKG
DLAIFGVVPDY
=,,i AA
(SEQ ID NO: 544) (SEQ ID NO: 545) (SEQ ID
NO: 546) AACTATGGCATGCAC GCTATATGGTTTGATGCAAGTGA
GATTTGGCGATTTTTGGAGTGGT
TAAATACTATGCAGACGCCGTGA CCCCGACTAC

NA
n ,--i AGGGC

.7r n (SEQ ID NO: 547) (SEQ ID NO: 548) (SEQ ID
NO: 549) =
cp NYGMH AIWFDASDKYYADAVKG
DLAIFGVVPDY w o (SEQ ID NO: 550) (SEQ ID NO: 551) (SEQ ID
NO: 552) oe 'a oe cr oe AACTATGGCATGCAC GCTATATGGTTTGATGCAAGTGA
GATATTGCGATTTTTGGAGTGTTT
NA TAAATACTATGCAGACGCCGTGA CCCGACTAC
rl AGGGC

=
n.) n (SEQ ID NO: 553) (SEQ ID NO: 554) (SEQ ID
NO: 555) o =
NYGMH AIWFDASDKYYADAVKG
DIAIFGVFPDY oe AA
i-J
(SEQ ID NO: 556) (SEQ ID NO: 557) (SEQ ID
NO: 558) c,.) o AACTATGGCATGCAC GCTATATGGTTTGATGCAAGTGA
GATATTGCGATTTTTGGAGTGTTT o TAAATACTATGCAGACGCCGTGA CCCGACTAC
NA
rl AGGGC
=
`z. (SEQ ID NO: 559) (SEQ ID NO: 560) (SEQ ID
NO: 561) =
NYGMH AIWFDASDKYYADAVKG
DIAIFGVFPDY

(SEQ ID NO: 562) (SEQ ID NO: 563) (SEQ ID
NO: 564) AACTATGGCATGCAC GCTATATGGTTTGATGCAAGTGA
GATATTGCGATTTTTGGAGTGGT
TAAATACTATGCAGACGCCGTGA CCCCGACTAC
NA
in AGGGC
rl P
n (SEQ ID NO: 565) (SEQ ID NO: 566) (SEQ ID
NO: 567) .

NYGMH AIWFDASDKYYADAVKG
DIAIFGVVPDY .
, (SEQ ID NO: 568) (SEQ ID NO: 569) (SEQ ID
NO: 570) ..' AACTATGGCATGCAC GCTATATGGTTTGATGCAAGTGA
GATATTGCGATTTTTGGAGTGGT .
, TAAATACTATGCAGACGCCGTGA CCCCGACTAC
' , NA
o re) AGGGC
' .7r , n (SEQ ID NO: 571) (SEQ ID NO: 572) (SEQ ID
NO: 573) =
NYGMH AIWFDASDKYYADAVKG
DIAIFGVVPDY

(SEQ ID NO: 574) (SEQ ID NO: 575) (SEQ ID
NO: 576) AACTATGGCATGCAC GCTATATGGTTTGATGCAAGTGA
GATATTGCGATTTTTGGAGTGTTT
TAAATACTATGCAGACGCCGTGA CCCGACTAC
NA
re) AGGGC
,--i fl (SEQ ID NO: 577) (SEQ ID NO: 578) (SEQ ID
NO: 579) NYGMH AIWFDASDKYYADAVKG
DIAIFGVFPDY n =,,i (SEQ ID NO: 580) (SEQ ID NO: 581) (SEQ ID
NO: 582) cp AACTATGGCATGCAC GCTATATGGTTTGATGCAAGTGA
GATATTGCGATTTTTGGAGTGTTT n.) ,--i o n TAAATACTATGCAGACGCCGTGA CCCGACTAC
oe NA
'a C.7 AGGGC
c,.) el r (SEQ ID NO: 583) (SEQ ID NO: 584) (SEQ ID
NO: 585) oe cr oe NYGMH AIWFDASDKYYADAVKG
DIAIFGVFPDY
AA
(SEQ ID NO: 586) (SEQ ID NO: 587) (SEQ ID
NO: 588) AACTATGGCATGCAC GCTATATGGTTTGATGCAAGTGA

n.) TAAATACTATGCAGACGCCGTGA CCCGACTAC
o NA
oe ,--i AGGGC
fl (SEQ ID NO: 589) (SEQ ID NO: 590) (SEQ ID
NO: 591) -4 =
o NYGMH AIWFDASDKYYADAVKG
DIAIFGVFPDY o AA

(SEQ ID NO: 592) (SEQ ID NO: 593) (SEQ ID
NO: 594) AACTATGGCATGCAC GCTATATGGTTTGATGCAAGTGA
GATATTGCGATTTTTGGAGTGAT
TAAATACTATGCAGACGCCGTGA CCCCGACTAC
NA
o AGGGC
=
fl (SEQ ID NO: 595) (SEQ ID NO: 596) (SEQ ID
NO: 597) =
NYGMH AIWFDASDKYYADAVKG
DIAIFGVIPDY

(SEQ ID NO: 598) (SEQ ID NO: 599) (SEQ ID
NO: 600) AACTATGGCATGCAC GCTATATGGTTTGATGCAAGTGA
GATATTGCGATTTTTGGAGTGAT p TAAATACTATGCAGACGCCGTGA CCCCGACTAC
NA .
o AGGGC .
=
, `z. (SEQ ID NO: 601) (SEQ ID NO: 602) (SEQ ID
NO: 603) ..
NYGMH AIWFDASDKYYADAVKG
DIAIFGVIPDY .
PI AA
, ,0 (SEQ ID NO: 604) (SEQ ID NO: 605) (SEQ ID
NO: 606) , , , AACTATGGCATGCAC GCTATATGGTTTGATGCAAGTGA
GATTTGGCGATTTTTGGAGTGGT
, TAAATACTATGCAGACGCCGTGA CCCCGACTAC
NA
N AGGGC
.7r fl (SEQ ID NO: 607) (SEQ ID NO: 608) (SEQ ID
NO: 609) NYGMH AIWFDASDKYYADAVKG
DLAIFGVVPDY
=,,i AA
(SEQ ID NO: 610) (SEQ ID NO: 611) (SEQ ID
NO: 612) AACTATGGCATGCAC GCTATATGGTTTGATGCAAGTGA
GATCAGGCGATTTTTGGAGTGGT
TAAATACTATGCAGACGCCGTGA CCCCGATTAC

NA
n x AGGGC
.7r fl (SEQ ID NO: 613) (SEQ ID NO: 614) (SEQ ID
NO: 615) =
cp NYGMH AIWFDASDKYYADAVKG
DQAIFGVVPDY w o (SEQ ID NO: 616) (SEQ ID NO: 617) (SEQ ID
NO: 618) oe 'a oe cr oe AACTATGGCATGCAC GCTATATGGTTTGATGCAAGTGA
GATATTGCGATTTTTGGAGTGGT
NA TAAATACTATGCAGACGCCGTGA CCCCGACTAC
o n (SEQ ID NO: 619) (SEQ ID NO: 620) (SEQ ID
NO: 621) o =
NYGMH AIWFDASDKYYADAVKG
DIAIFGVVPDY oe AA
i-J
(SEQ ID NO: 622) (SEQ ID NO: 623) (SEQ ID
NO: 624) c,.) o AACTATGGCATGCAC GCTATATGGTTTGATGCAAGTGA
GATTTGGCGATTTTTGGAGTGGT o TAAATACTATGCAGACGCCGTGA CCCCGACTAC
NA
N AGGGC
.7r `z. (SEQ ID NO: 625) (SEQ ID NO: 626) (SEQ ID
NO: 627) =
NYGMH AIWFDASDKYYADAVKG
DLAIFGVVPDY

(SEQ ID NO: 628) (SEQ ID NO: 629) (SEQ ID
NO: 630) AACTATGGCATGCAC GCTATATGGTTTGATGCAAGTGA
GATCAGGCGATTTTTGGAGTGGT
TAAATACTATGCAGACGCCGTGA CCCCGATTAC
NA
o AGGGC
.7r P
`z. (SEQ ID NO: 631) (SEQ ID NO: 632) (SEQ ID
NO: 633) .

NYGMH AIWFDASDKYYADAVKG
DQAIFGVVPDY .
, (SEQ ID NO: 634) (SEQ ID NO: 635) (SEQ ID
NO: 636) ..' AACTATGGCATGCAC GCTATATGGTTTGATGCAAGTGA
GATTTGGCGATTTTTGGAGTGGT .
, TAAATACTATGCAGACGCCGTGA CCCCGACTAC
' , NA
o in AGGGC
' = , n (SEQ ID NO: 637) (SEQ ID NO: 638) (SEQ ID
NO: 639) =
NYGMH AIWFDASDKYYADAVKG
DLAIFGVVPDY

(SEQ ID NO: 640) (SEQ ID NO: 641) (SEQ ID
NO: 642) AACTATGGCATGCAC GCTATATGGTTTGATGCAAGTGA
GATTTGGCGATTTTTGGAGTGGT
TAAATACTATGCAGACGCCGTGA CCCCGACTAC
NA
in AGGGC
=
`z. (SEQ ID NO: 643) (SEQ ID NO: 644) (SEQ ID
NO: 645) NYGMH AIWFDASDKYYADAVKG
DLAIFGVVPDY n =,,i (SEQ ID NO: 646) (SEQ ID NO: 647) (SEQ ID
NO: 648) cp .7r AACTATGGCATGCAC GCTATATGGTTTGATGCAAGTGA
GATATTGCGATTTTTGGAGTGGT n.) o n TAAATACTATGCAGACGCCGTGA CCCCGACTAC
oe NA
'a C.7 AGGGC
c,.) c4 c (SEQ ID NO: 649) (SEQ ID NO: 650) (SEQ ID
NO: 651) oe cr oe NYGMH AIWFDASDKYYADAVKG
DIAIFGVVPDY
AA
(SEQ ID NO: 652) (SEQ ID NO: 653) (SEQ ID
NO: 654) AACTATGGCATGCAC GCTATATGGTTTGATGCAAGTGA

n.) TAAATACTATGCAGACGCCGTGA CCCCGACTAC
o NA
oe .7r AGGGC
re) W
fl (SEQ ID NO: 655) (SEQ ID NO: 656) (SEQ ID
NO: 657) -4 =
o NYGMH AIWFDASDKYYADAVKG
DLAIFGVVPDY o AA

(SEQ ID NO: 658) (SEQ ID NO: 659) (SEQ ID
NO: 660) AACTATGGCATGCAC GCTATATGGTTTGATGCAAGTGA
GATATTGCGATTTTTGGAGTGGT
TAAATACTATGCAGACGCCGTGA CCCCGACTAC
NA
o AGGGC
re) fl (SEQ ID NO: 661) (SEQ ID NO: 662) (SEQ ID
NO: 663) =
NYGMH AIWFDASDKYYADAVKG
DIAIFGVVPDY

(SEQ ID NO: 664) (SEQ ID NO: 665) (SEQ ID
NO: 666) AACTATGGCATGCAC GCTATATGGTTTGATGCGTACGG
GATCAGACGATTTTTGGAGTGGT p TAAATACTATGCAGACGCCGTGA CCCCGACTAC
NA .
N AGGGC
.
=
, fl (SEQ ID NO: 667) (SEQ ID NO: 668) (SEQ ID
NO: 669) ..
NYGMH AIWFDAYGKYYADAVKG
DQTIFGVVPDY
PI AA
, ,0 (SEQ ID NO: 670) (SEQ ID NO: 671) (SEQ ID
NO: 672) , , , AACTATGGCATGCAC GCTATATGGTTTGATGCGTACGG
GATCAGACGATTTTTGGAGTGGT
, TAAATACTATGCAGACGCCGTGA CCCCGACTAC
NA
N AGGGC
=
`z. (SEQ ID NO: 673) (SEQ ID NO: 674) (SEQ ID
NO: 675) NYGMH AIWFDAYGKYYADAVKG
DQTIFGVVPDY
=,,i AA
(SEQ ID NO: 676) (SEQ ID NO: 677) (SEQ ID
NO: 678) AACTATGGCATGCAC GCTATATGGTTTGATGCGTACGG
GATAAGACGATTTTTGGAGTGGT
TAAATACTATGCAGACGCCGTGA CCCCGACTAC

NA
n ,--i AGGGC

fl (SEQ ID NO: 679) (SEQ ID NO: 680) (SEQ ID
NO: 681) =
cp NYGMH AIWFDAYGKYYADAVKG
DKTIFGVVPDY w o (SEQ ID NO: 682) (SEQ ID NO: 683) (SEQ ID
NO: 684) oe 'a oe cr oe AACTATGGCATGCAC GCTATATGGTTTGATGCGTACGG
GATAAGACGATTTTTGGAGTGGT
NA TAAATACTATGCAGACGCCGTGA CCCCGACTAC
AGGGC

n (SEQ ID NO: 685) (SEQ ID NO: 686) (SEQ ID
NO: 687) o =
NYGMH AIWFDAYGKYYADAVKG
DKTIFGVVPDY oe AA
i-J
(SEQ ID NO: 688) (SEQ ID NO: 689) (SEQ ID
NO: 690) c,.) o AACTATGGCATGCAC GCTATATGGTTTGATGCGTACGG
GATAAGACGATTTTTGGAGTGGT o TAAATACTATGCAGACGCCGTGA CCCCGACTAC
NA
o AGGGC
,--i n (SEQ ID NO: 691) (SEQ ID NO: 692) (SEQ ID
NO: 693) =
NYGMH AIWFDAYGKYYADAVKG
DKTIFGVVPDY

(SEQ ID NO: 694) (SEQ ID NO: 695) (SEQ ID
NO: 696) AACTATGGCATGCAC GCTATATGGTTTGATGCGTACGA
GATAAGTCGATTTTTGGAGTGGT
CAAATACTATGCAGACGCCGTGA CCCCGACTAC
NA
AGGGC
re) P
n (SEQ ID NO: 697) (SEQ ID NO: 698) (SEQ ID
NO: 699) .

NYGMH AIWFDAYDKYYADAVKG
DKSIFGVVPDY .
, (SEQ ID NO: 700) (SEQ ID NO: 701) (SEQ ID
NO: 702) ..' AACTATGGCATGCAC GCTATATGGTTTGATGCGTACGA
GATAAGTCGATTTTTGGAGTGGT .
, CAAATACTATGCAGACGCCGTGA CCCCGACTAC
' , NA
o in AGGGC
' .7r , n (SEQ ID NO: 703) (SEQ ID NO: 704) (SEQ ID
NO: 705) =
NYGMH AIWFDAYDKYYADAVKG
DKSIFGVVPDY

(SEQ ID NO: 706) (SEQ ID NO: 707) (SEQ ID
NO: 708) AACTATGGCATGCAC GCTATATGGTTTGATGCGTACGA
GATCTCGCGATTTTTGGAGTGGT
CAAATACTATGCAGACGCCGTGA CCCCGACTAC
NA
in AGGGC
rn n (SEQ ID NO: 709) (SEQ ID NO: 710) (SEQ ID
NO: 711) NYGMH AIWFDAYDKYYADAVKG
DLAIFGVVPDY n =,,i (SEQ ID NO: 712) (SEQ ID NO: 713) (SEQ ID
NO: 714) cp re) AACTATGGCATGCAC GCTATATGGTTTGATGCGGCTTT
GATCTCGCGATTTTTGGAGTGGT n.) o n CAAATACTATGCAGACGCCGTGA CCCCGACTAC
oe NA
'a C.7 AGGGC
c,.) c4 c (SEQ ID NO: 715) (SEQ ID NO: 716) (SEQ ID
NO: 717) oe cr oe NYGMH AIWFDAAFKYYADAVKG
DLAIFGVVPDY
AA
(SEQ ID NO: 718) (SEQ ID NO: 719) (SEQ ID
NO: 720) NYGMH AIWFDASDKYYADAVKG

iPS:529381 AA
n.) o (SEQ ID NO: 1293) (SEQ ID NO: 1294) (SEQ ID
NO: 1295) 1¨, oe NYGMH AIWFDASDKYYADAVKG
DIAIFGVVPDY
iPS:529382 AA
c,.) (SEQ ID NO: 1303) (SEQ ID NO: 1304) (SEQ ID
NO: 1305) -4 o o NYGMH AIWFDASDKYYADAVKG

iPS:529397 AA
(SEQ ID NO: 1313) (SEQ ID NO: 1314) (SEQ ID
NO: 1315) NYGMH AIWFDASDKYYADAVKG
DLAIFGVIPDY
iPS:529399 AA
(SEQ ID NO: 1323) (SEQ ID NO: 1324) (SEQ ID
NO: 1325) NYGMH AIWFDASDKYYADAVKG
DIAIFGVVPDY
iPS:529400 AA
(SEQ ID NO: 1333) (SEQ ID NO: 1334) (SEQ ID
NO: 1335) NYGMH AIWFDASDKYYADAVKG
DLAIFGVVPDY
iPS:529403 AA
(SEQ ID NO: 1343) (SEQ ID NO: 1344) (SEQ ID
NO: 1345) P
NYGMH AIWFDASDKYYADAVKG
DLAIFGVVPDY .
iPS:529404 AA
.
(SEQ ID NO: 1353) (SEQ ID NO: 1354) (SEQ ID
NO: 1355) .
, NYGMH AIWFDASDKYYADAVKG DLAIFGVVPDY
' iPS:529405 AA ,, (SEQ ID NO: 1363) (SEQ ID NO: 1364) (SEQ ID
NO: 1365) .
, , , .
, , Iv n ,-i cp t.., =
oe 'a oe c:
oe Table 5. Exemplary Light and Heavy Chain Nucleic Acid ("NA") and Amino Acid ("AA") Sequences Ab Description Type LC HC
oe GAAATAGTGATGACGCAGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
CCAGCCACCCTGTCTGTGTCT TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGGATTCA
CCAGGGGAAAGAGCCACCCT CCTTCAGTAACTATGGCATGCACTGGGTCCGCCAGGCTCCA
CTCCTGCAGGGCCAGTCAGAG GGCGAGGGGCTGGAGTGGGTGGCAGCTATATGGTTTGATGC
TGTTGATAGACACTTAGCCTG AAGTGATAAATACTATGCAGACGCCGTGAAGGGCCGATTCA
GTACCAGCAGAAACCTGGCC CCATCTCCAGAGACAACTCCAAGAACACGCTGTATCTGCAA
AGGCTCCCAGGCTCCTCATCT ATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTG
ACGAAGCAGCCACCAGGGCC TGCGAGAGATTTGGCGATTTTTGGAGTGGTCCCCGACTACT
[hu anti- ACTGGTATCCCAGCCAGGTTC
GGGGCCAGGGAACCCTGGTCACCGTGTCTAGTGCCTCCACC
<huGIPR> AGTGGCAGTGGGTCTGGGAC
AAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAG
2G10.303 AGAGTTCACTCTCACCATCAG
CACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGG
VK3 (1-236) CAGCCTGCAGTCTGAAGATTT
ACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
VL]::huKLC TGCAGTTTATTACTGTCAGCA
GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
-CL + GTATCAGAACTGGCCTCTCAC
GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC
[Unknown TTTCGGCGGAGGGACCAAGGT
CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTG
anti-A N GGAGATCAAACGAACGGTGG
AATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTG
<huGIPR> CTGCACCATCTGTCTTCATCTT
AGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGC
2G10.610 CCCGCCATCTGATGAGCAGTT
CCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTC
VH3 (1-472) GAAATCTGGAACTGCCTCTGT
CCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCC
VH]::huIgG1 TGTGTGCCTGCTGAATAACTT
TGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACC
zSEFL2-2 CTATCCCAGAGAGGCCAAAG
CTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTG
(mAb); LMR TACAGTGGAAGGTGGATAAC
CATAATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCA
ID: SS- GCCCTCCAATCGGGTAACTCC
GCACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAG

GACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCA
GGACAGCAAGGACAGCACCT ACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAA
ACAGCCTCAGCAGCACCCTGA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCC
1-d CGCTGAGCAAAGCAGACTAC CCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTG
GAGAAACACAAAGTCTACGC ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGT
CTGCGAAGTCACCCATCAGGG GGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAG
CCTGAGCTCGCCCGTCACAAA ACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTC
ri GAGCTTCAACAGGGGAGAGT
TATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGG
oe GT
GGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCAC c7, oe AACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAA
A
(SEQ ID NO: 12) (SEQ ID NO: 13) EIVMTQ SP ATL SVSPGERATLS QVQLVE SGGGVVQPGRSLRL SCAASGFTFSNYGMHWVRQAP
CRASQSVDRHLAWYQQKPGQ GEGLEWVAAIWFDASDKYYADAVKGRFTISRDNSKNTLYLQ
oe APRLLIYEAATRATGIPARFSGS MNSLRAEDTAVYYCARDLAIFGVVPDYWGQGTLVTVSSASTK
GS GTEFTL TI S SLQ SEDFAVYYC GP SVFPL AP S SKST S GGTAALGCLVKDYFPEPVTVSWN S
GAL T
QQYQNWPLTFGGGTKVEIKRT SGVHTFPAVLQSSGLY SLSSVVTVP SSSLGTQTYICNVNHKP SN
VAAPSVFIFPPSDEQLKSGTASV TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
AA
VCLLNNFYPREAKVQWKVDN MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCE
ALQSGNSQESVTEQDSKDSTYS EQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
L SSTLTL SKADYEKHKVYACE SKAKGQPREPQVYTLPP SREEMTKNQVSLTCLVKGFYP SDIAV
VTHQGLSSPVTKSFNRGEC
EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN
VFSCSVMHEALHNHYTQKSLSLSPGK
(SEQ ID NO: 14) (SEQ ID NO: 15) GAAATAGTGATGACGCAGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
CCAGCCACCCTGTCTGTGTCT TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGGATTCA
CCAGGGGAAAGAGCCACCCT CCTTCAGTAACTATGGCATGCACTGGGTCCGCCAGGCTCCA
[hu anti-h CTCCTGCAGGGCCAGTCAGAG
GGCGAGGGGCTGGAGTGGGTGGCAGCTATATGGTTTGATGC
<uGIPR>
TGTTAACAGACACTTAGCCTG AAGTGATAAATACTATGCAGACGCCGTGAAGGGCCGATTCA
2G10.304 GTACCAGCAGAAACCTGGCC CCATCTCCAGAGACAACTCCAAGAACACGCTGTATCTGCAA
( 1-236) VL AGGCTCCCAGGCTCCTCATCT
ATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTG
]::huKLC
ACGAAGCAGCCACCAGGGCC TGCGAGAGATTTGGCGATTTTTGGAGTGGTCCCCGACTACT
-CL +
ACTGGTATCCCAGCCAGGTTC GGGGCCAGGGAACCCTGGTCACCGTGTCTAGTGCCTCCACC
[Unknown AGTGGCAGTGGGTCTGGGAC AAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAG
anti-NA AGAGTTCACTCTCACCATCAG CACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGG
<huGIPR>

ACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
.
TGCAGTTTATTACTGTCAGCA GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
VH3 (1-472) GTATCAGAACTGGCCTCTCAC GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC
VH1::ImIgG1 TTTCGGCGGAGGGACCAAGGT CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTG
zSEFL2-2 GGAGATCAAACGAACGGTGG AATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTG

(mAb); LMR
CTGCACCATCTGTCTTCATCTT AGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGC
f 1 26181 CCCGCCATCTGATGAGCAGTT
CCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTC
GAAATCTGGAACTGCCTCTGT CCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCC
TGTGTGCCTGCTGAATAACTT TGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACC
CTATCCCAGAGAGGCCAAAG CTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTG
oe cr oe TACAGTGGAAGGTGGATAAC CATAATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCA
GCCCTCCAATCGGGTAACTCC GCACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAG
CAGGAGAGTGTCACAGAGCA GACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCA
GGACAGCAAGGACAGCACCT ACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAA
ACAGCCTCAGCAGCACCCTGA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCC
CGCTGAGCAAAGCAGACTAC CCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTG
GAGAAACACAAAGTCTACGC ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGT
CTGCGAAGTCACCCATCAGGG GGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAG
CCTGAGCTCGCCCGTCACAAA ACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTC
GAGCTTCAACAGGGGAGAGT TATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGG
GT
GGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCAC
AACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAA
A
(SEQ ID NO: 16) (SEQ ID NO: 17) EIVMTQ SP ATL SVSPGERATLS QVQLVE SGGGVVQPGRSLRL SCAASGFTFSNYGMHWVRQAP
CRASQSVNRHLAWYQQKPGQ GEGLEWVAAIWFDASDKYYADAVKGRFTISRDNSKNTLYLQ
APRLLIYEAATRATGIPARFSGS MNSLRAEDTAVYYCARDLAIFGVVPDYWGQGTLVTVSSASTK
GS GTEFTL TI S SLQSEDFAVYYC GP SVFPL AP S SKST S GGTAALGCLVKDYFPEPVTVSWN S GAL
T
QQYQNWPLTFGGGTKVEIKRT SGVHTFPAVLQS SGLY SLS SVVTVP S S SLGTQTYICNVNHKP SN
AA VAAPSVFIFPPSDEQLKSGTASV TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
VCLLNNFYPREAKVQWKVDN MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCE
ALQSGNSQESVTEQD SKD STY S EQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
L SSTLTL SKADYEKHKVYACE SKAKGQPREPQVYTLPP SREEMTKNQVSLTCLVKGFYP SDIAV
VTHQGLSSPVTKSFNRGEC EWE SNGQPENNYKTTPPVLD SD
GSFFLY SKL TVD KSRWQQ GN
VFSCSVMHEALHNHYTQKSLSLSPGK
(SEQ ID NO: 18) (SEQ ID NO: 19) [hu anti- GAAATAGTGATGACGCAGTCT
CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
<huGIPR> CCAGCCACCCTGTCTGTGTCT
TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGGATTCA
2G10.323 CCAGGGGAAAGAGCCACCCT
CCTTCAGTAACTATGGCATGCACTGGGTCCGCCAGGCTCCA
VK3 (1-236) CTCCTGCAGGGCCAGTCAGAG
GGCGAGGGGCTGGAGTGGGTGGCAGCTATATGGTTTGATGC
VL]::huKLC NA TGTTCATAGACACTTAGCCTG AAGTGATAAATACTATGCAGACGCCGTGAAGGGCCGATTCA

-CL + GTACCAGCAGAAACCTGGCC
CCATCTCCAGAGACAACTCCAAGAACACGCTGTATCTGCAA
PI [Unknown AGGCTCCCAGGCTCCTCATCT
ATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTG
g anti- ACGAAGCAGCCACCAGGGCC
TGCGAGAGATTTGGCGATTTTTGGAGTGGTCCCCGACTACT
<huGIPR> ACTGGTATCCCAGCCAGGTTC
GGGGCCAGGGAACCCTGGTCACCGTGTCTAGTGCCTCCACC
2G10.610 AGTGGCAGTGGGTCTGGGAC
AAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAG oe oe VH3 (1-472) AGAGTTCACTCTCACCATCAG
CACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGG
VH]::huIgG1 CAGCCTGCAGTCTGAAGATTT
ACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
zSEFL2-2 TGCAGTTTATTACTGTCAGCA
GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
(mAb); LMR GTATCAGAACTGGCCTCTCAC
GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC
ID: SS- TTTCGGCGGAGGGACCAAGGT
CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTG

AATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTG
CTGCACCATCTGTCTTCATCTT AGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGC
CCCGCCATCTGATGAGCAGTT CCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTC
GAAATCTGGAACTGCCTCTGT CCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCC
TGTGTGCCTGCTGAATAACTT TGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACC
CTATCCCAGAGAGGCCAAAG CTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTG
TACAGTGGAAGGTGGATAAC CATAATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCA
GCCCTCCAATCGGGTAACTCC GCACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAG
CAGGAGAGTGTCACAGAGCA GACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCA
GGACAGCAAGGACAGCACCT ACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAA
ACAGCCTCAGCAGCACCCTGA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCC
CGCTGAGCAAAGCAGACTAC CCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTG
GAGAAACACAAAGTCTACGC ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGT
CTGCGAAGTCACCCATCAGGG GGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAG
CCTGAGCTCGCCCGTCACAAA ACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTC
GAGCTTCAACAGGGGAGAGT TATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGG
GT
GGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCAC
AACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAA
A
(SEQ ID NO: 20) (SEQ ID NO: 21) EIVMTQSPATLSVSPGERATLS QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMHWVRQAP
CRASQSVHRHLAWYQQKPGQ GEGLEWVAAIWFDASDKYYADAVKGRFTISRDNSKNTLYLQ
APRLLIYEAATRATGIPARFSGS MNSLRAEDTAVYYCARDLAIFGVVPDYWGQGTLVTVSSASTK
GSGTEFTLTISSLQSEDFAVYYC GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALT
QQYQNWPLTFGGGTKVEIKRT SGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN
AA VAAPSVFIFPPSDEQLKSGTASV TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL

VCLLNNFYPREAKVQWKVDN MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCE
ALQSGNSQESVTEQDSKDSTYS EQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
LSSTLTLSKADYEKHKVYACE SKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAV
oe VTHQGLSSPVTKSFNRGEC
EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN
VFSCSVMHEALHNHYTQKSLSLSPGK
oe oe (SEQ ID NO: 22) (SEQ ID NO: 23) GAAATAGTGATGACGCAGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
CCAGCCACCCTGTCTGTGTCT TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGGATTCA
CCAGGGGAAAGAGCCACCCT CCTTCAGTAACTATGGCATGCACTGGGTCCGCCAGGCTCCA
CTCCTGCAGGGCCAGTCAGAG GGCGAGGGGCTGGAGTGGGTGGCAGCTATATGGTTTGATGC
oe TGTTGAAAGACACTTAGCCTG AAGTGATAAATACTATGCAGACGCCGTGAAGGGCCGATTCA
GTACCAGCAGAAACCTGGCC CCATCTCCAGAGACAACTCCAAGAACACGCTGTATCTGCAA
AGGCTCCCAGGCTCCTCATCT ATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTG
ACGAAGCAGCCACCAGGGCC TGCGAGAGATTTGGCGATTTTTGGAGTGGTCCCCGACTACT
ACTGGTATCCCAGCCAGGTTC GGGGCCAGGGAACCCTGGTCACCGTGTCTAGTGCCTCCACC
AGTGGCAGTGGGTCTGGGAC AAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAG
[hu anti-AGAGTTCACTCTCACCATCAG CACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGG
<huGIPR>
CAGCCTGCAGTCTGAAGATTT ACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
2G10.309 TGCAGTTTATTACTGTCAGCA GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
VK3 (1-236) GTATCAGAACTGGCCTCTCAC GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC
VL]::huKLC
TTTCGGCGGAGGGACCAAGGT CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTG
-CL +
GGAGATCAAACGAACGGTGG AATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTG
[Unknown CTGCACCATCTGTCTTCATCTT AGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGC
anti-NA CCCGCCATCTGATGAGCAGTT CCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTC
<huGIPR>
GAAATCTGGAACTGCCTCTGT CCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCC
2G10.610 VH3( 1-472) TGTGTGCCTGCTGAATAACTT TGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACC
CTATCCCAGAGAGGCCAAAG CTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTG
VH]::huIgG1 TACAGTGGAAGGTGGATAAC CATAATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCA
zSEFL2-2 GCCCTCCAATCGGGTAACTCC GCACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAG
(m b), LMR
CAGGAGAGTGTCACAGAGCA GACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCA
ID: SS-GGACAGCAAGGACAGCACCT ACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAA

ACAGCCTCAGCAGCACCCTGA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCC
CGCTGAGCAAAGCAGACTAC CCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTG
GAGAAACACAAAGTCTACGC ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGT
CTGCGAAGTCACCCATCAGGG GGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAG
CCTGAGCTCGCCCGTCACAAA ACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTC

GAGCTTCAACAGGGGAGAGT TATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGG
GT
GGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCAC
AACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAA
oe A
(SEQ ID NO: 24) (SEQ ID NO: 25) oe oe EIVMTQSPATLSVSPGERATLS QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMHWVRQAP
CRASQSVERHLAWYQQKPGQ GEGLEWVAAIWFDASDKYYADAVKGRFTISRDNSKNTLYLQ
APRLLIYEAATRATGIPARFSGS MNSLRAEDTAVYYCARDLAIFGVVPDYWGQGTLVTVSSASTK
GSGTEFTLTISSLQSEDFAVYYC GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALT
QQYQNWPLTFGGGTKVEIKRT SGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN
AA VAAPSVFIFPPSDEQLKSGTASV TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
VCLLNNFYPREAKVQWKVDN MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCE
ALQSGNSQESVTEQDSKDSTYS EQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
LSSTLTLSKADYEKHKVYACE SKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAV
VTHQGLSSPVTKSFNRGEC
EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN
VFSCSVMHEALHNHYTQKSLSLSPGK
(SEQ ID NO: 26) (SEQ ID NO: 27) GAAATAGTGATGACGCAGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
CCAGCCACCCTGTCTGTGTCT TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGGATTCA
CCAGGGGAAAGAGCCACCCT CCTTCAGTAACTATGGCATGCACTGGGTCCGCCAGGCTCCA
CTCCTGCAGGGCCAGTCAGAG GGCGAGGGGCTGGAGTGGGTGGCAGCTATATGGTTTGATGC
[hu anti- TGTTTTCAGACACTTAGCCTG
AAGTGATAAATACTATGCAGACGCCGTGAAGGGCCGATTCA
<huGIPR> GTACCAGCAGAAACCTGGCC
CCATCTCCAGAGACAACTCCAAGAACACGCTGTATCTGCAA
2G10.316 AGGCTCCCAGGCTCCTCATCT
ATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTG
VK3 (1-236) ACGAAGCAGCCACCAGGGCC
TGCGAGAGATTTGGCGATTTTTGGAGTGGTCCCCGACTACT
VL]::huKLC ACTGGTATCCCAGCCAGGTTC
GGGGCCAGGGAACCCTGGTCACCGTGTCTAGTGCCTCCACC
-CL + AGTGGCAGTGGGTCTGGGAC
AAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAG
[Unknown AGAGTTCACTCTCACCATCAG
CACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGG
anti- NA CAGCCTGCAGTCTGAAGATTT
ACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
<huGIPR> TGCAGTTTATTACTGTCAGCA
GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
2G10.610 GTATCAGAACTGGCCTCTCAC
GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC
VH3 (1-472) TTTCGGCGGAGGGACCAAGGT
CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTG
VH]::huIgG1 GGAGATCAAACGAACGGTGG
AATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTG
zSEFL2-2 CTGCACCATCTGTCTTCATCTT
AGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGC
(mAb); LMR CCCGCCATCTGATGAGCAGTT
CCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTC
ID: SS- GAAATCTGGAACTGCCTCTGT
CCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCC

TGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACC
CTATCCCAGAGAGGCCAAAG CTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTG
TACAGTGGAAGGTGGATAAC CATAATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCA
oe GCCCTCCAATCGGGTAACTCC GCACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAG
CAGGAGAGTGTCACAGAGCA GACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCA
oe oe GGACAGCAAGGACAGCACCT ACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAA
ACAGCCTCAGCAGCACCCTGA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCC
CGCTGAGCAAAGCAGACTAC CCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTG
GAGAAACACAAAGTCTACGC ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGT
CTGCGAAGTCACCCATCAGGG GGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAG
CCTGAGCTCGCCCGTCACAAA ACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTC
GAGCTTCAACAGGGGAGAGT TATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGG
GT
GGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCAC
AACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAA
A
(SEQ ID NO: 28) (SEQ ID NO: 29) EIVMTQSPATL SVSPGERATLS QVQLVE SGGGVVQPGRSLRL SCAASGFTFSNYGMHWVRQAP
CRASQSVFRHLAWYQQKPGQA GEGLEWVAAIWFDASDKYYADAVKGRFTISRDNSKNTLYLQ
PRLLIYEAATRATGIPARFSGSG MNSLRAEDTAVYYCARDLAIFGVVPDYWGQGTLVTVSSASTK
SGTEFTLTISSLQSEDFAVYYCQ GP SVFPLAP S SKST S GGTAALGCLVKDYFPEPVTVSWN S GALT
QYQNWPLTFGGGTKVEIKRTV SGVHTFPAVLQSSGLY SLSSVVTVP SSSLGTQTYICNVNHKP SN
AA AAP SVFIFPP SDEQLKSGTASVV
TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
CLLNNFYPREAKVQWKVDNAL MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCE
QSGNSQESVTEQD SKD STY SL S EQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
STLTLSKADYEKHKVYACEVT SKAKGQPREPQVYTLPP SREEMTKNQVSLTCLVKGFYP SDIAV
HQGL SSPVTKSFNRGEC
EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN
VFSCSVMHEALHNHYTQKSLSLSPGK
(SEQ ID NO: 30) (SEQ ID NO: 31) [hu anti- GAAATAGTGATGACGCAGTCT
CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
<huGIPR> CCAGCCACCCTGTCTGTGTCT
TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGGATTCA
2G10.604 CCAGGGGAAAGAGCCACCCT
CCTTCAGTAACTATGGCATGCACTGGGTCCGCCAGGCTCCA
VK3 (1-236) CTCCTGCAGGGCCAGTCAGAG
GGCGAGGGGCTGGAGTGGGTGGCAGCTATATGGTTTGATGC
VL]::huKLC TGTTAACAGACACTTAGCCTG
AAGTGATAAATACTATGCAGACGCCGTGAAGGGCCGATTCA
-CL + GTACCAGCAGAAACCTGGCC
CCATCTCCAGAGACAACTCCAAGAACACGCTGTATCTGCAA
[Unknown NA AGGCTCCCAGGCTCCTCATCT ATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTG
anti- ACGAAGCAGCCACCAGGGCC

<huGIPR> ACTGGTATCCCAGCCAGGGTC
GGGGCCAGGGAACCCTGGTCACCGTGTCTAGTGCCTCCACC
2G10.610 AGTGGCAGTGGGTCTGGGAC
AAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAG
c5 VH3 (1-472) AGAGTTCACTCTCACCATCAG
CACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGG
VH]::huIgG1 CAGCCTGCAGTCTGAAGATTT
ACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
zSEFL2-2 TGCAGTTTATTACTGTCAGCA
GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA oe oe (mAb); LMR GTATCAGAACTGGCCTCTCAC
GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC
ID: SS- TTTCGGCGGAGGGACCAAGGT
CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTG

AATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTG
CTGCACCATCTGTCTTCATCTT AGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGC
CCCGCCATCTGATGAGCAGTT CCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTC
GAAATCTGGAACTGCCTCTGT CCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCC
TGTGTGCCTGCTGAATAACTT TGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACC
CTATCCCAGAGAGGCCAAAG CTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTG
TACAGTGGAAGGTGGATAAC CATAATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCA
GCCCTCCAATCGGGTAACTCC GCACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAG
CAGGAGAGTGTCACAGAGCA GACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCA
GGACAGCAAGGACAGCACCT ACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAA
ACAGCCTCAGCAGCACCCTGA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCC
CGCTGAGCAAAGCAGACTAC CCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTG
GAGAAACACAAAGTCTACGC ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGT
CTGCGAAGTCACCCATCAGGG GGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAG
CCTGAGCTCGCCCGTCACAAA ACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTC
GAGCTTCAACAGGGGAGAGT TATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGG
GT
GGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCAC
AACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAA
A
(SEQ ID NO: 32) (SEQ ID NO: 33) EIVMTQSPATLSVSPGERATLS QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMHWVRQAP
CRASQSVNRHLAWYQQKPGQ GEGLEWVAAIWFDASDKYYADAVKGRFTISRDNSKNTLYLQ
APRLLIYEAATRATGIPARVSGS MNSLRAEDTAVYYCARDLAIFGVVPDYWGQGTLVTVSSASTK
GSGTEFTLTISSLQSEDFAVYYC GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALT
QQYQNWPLTFGGGTKVEIKRT SGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN
VAAPSVFIFPPSDEQLKSGTASV TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
AA
VCLLNNFYPREAKVQWKVDN MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCE
ALQSGNSQESVTEQDSKDSTYS EQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
LSSTLTLSKADYEKHKVYACE SKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAV

VTHQGLSSPVTKSFNRGEC
EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN
VFSCSVMHEALHNHYTQKSLSLSPGK
(SEQ ID NO: 34) (SEQ ID NO: 35) oe [hu anti-NA GAAATAGTGATGACGCAGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
" <huGIPR> CCAGCCACCCTGTCTGTGTCT
TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGGATTCA oe oe 2G10.609 CCAGGGGAAAGAGCCACCCT
CCTTCAGTAACTATGGCATGCACTGGGTCCGCCAGGCTCCA
VK3 (1-236) CTCCTGCAGGGCCAGTCAGAG
GGCGAGGGGCTGGAGTGGGTGGCAGCTATATGGTTTGATGC
VL]::huKLC TGTTGAAAGACACTTAGCCTG
AAGTGATAAATACTATGCAGACGCCGTGAAGGGCCGATTCA
-CL + GTACCAGCAGAAACCTGGCC
CCATCTCCAGAGACAACTCCAAGAACACGCTGTATCTGCAA
[Unknown AGGCTCCCAGGCTCCTCATCT
ATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTG
anti- ACGAAGCAGCCACCAGGGCC
TGCGAGAGATTTGGCGATTTTTGGAGTGGTCCCCGACTACT
<huGIPR> ACTGGTATCCCAGCCAGGGTC
GGGGCCAGGGAACCCTGGTCACCGTGTCTAGTGCCTCCACC
2G10.610 AGTGGCAGTGGGTCTGGGAC
AAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAG
VH3 (1-472) AGAGTTCACTCTCACCATCAG
CACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGG
VH]::huIgG1 CAGCCTGCAGTCTGAAGATTT
ACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
zSEFL2-2 TGCAGTTTATTACTGTCAGCA
GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
(mAb); LMR GTATCAGAACTGGCCTCTCAC
GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC
ID: SS- TTTCGGCGGAGGGACCAAGGT
CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTG

AATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTG
CTGCACCATCTGTCTTCATCTT AGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGC
CCCGCCATCTGATGAGCAGTT CCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTC
GAAATCTGGAACTGCCTCTGT CCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCC
TGTGTGCCTGCTGAATAACTT TGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACC
CTATCCCAGAGAGGCCAAAG CTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTG
TACAGTGGAAGGTGGATAAC CATAATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCA
GCCCTCCAATCGGGTAACTCC GCACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAG
CAGGAGAGTGTCACAGAGCA GACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCA
GGACAGCAAGGACAGCACCT ACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAA
ACAGCCTCAGCAGCACCCTGA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCC
CGCTGAGCAAAGCAGACTAC CCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTG
GAGAAACACAAAGTCTACGC ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGT
CTGCGAAGTCACCCATCAGGG GGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAG
CCTGAGCTCGCCCGTCACAAA ACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTC
GAGCTTCAACAGGGGAGAGT TATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGG
GT
GGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCAC
AACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAA

A
(SEQ ID NO: 36) (SEQ ID NO: 37) EIVMTQSPATLSVSPGERATLS QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMHWVRQAP
oe AA CRASQSVERHLAWYQQKPGQ GEGLEWVAAIWFDASDKYYADAVKGRFTISRDNSKNTLYLQ
APRLLIYEAATRATGIPARVSGS MNSLRAEDTAVYYCARDLAIFGVVPDYWGQGTLVTVSSASTK
oe oe GSGTEFTLTISSLQSEDFAVYYC GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALT
QQYQNWPLTFGGGTKVEIKRT SGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN
VAAPSVFIFPPSDEQLKSGTASV TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
VCLLNNFYPREAKVQWKVDN MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCE
ALQSGNSQESVTEQDSKDSTYS EQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
LSSTLTLSKADYEKHKVYACE SKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAV
VTHQGLSSPVTKSFNRGEC
EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN
VFSCSVMHEALHNHYTQKSLSLSPGK
(SEQ ID NO: 38) (SEQ ID NO: 39) GAAATAGTGATGACGCAGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
CCAGCCACCCTGTCTGTGTCT TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGGATTCA
CCAGGGGAAAGAGCCACCCT CCTTCAGTAACTATGGCATGCACTGGGTCCGCCAGGCTCCA
CTCCTGCAGGGCCAGTCAGAG GGCGAGGGGCTGGAGTGGGTGGCAGCTATATGGTTTGATGC
TGTTGATAGACACTTAGCCTG AAGTGATAAATACTATGCAGACGCCGTGAAGGGCCGATTCA
h GTACCAGCAGAAACCTGGCC
CCATCTCCAGAGACAACTCCAAGAACACGCTGTATCTGCAA
R>
[u anti-AGGCTCCCAGGCTCCTCATCT ATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTG
<huGIP
2G10.603 ACGAAGCAGCCACCAGGGCC
TGCGAGAGATTTGGCGATTTTTGGAGTGGTCCCCGACTACT
ACTGGTATCCCAGCCAGGGTC GGGGCCAGGGAACCCTGGTCACCGTGTCTAGTGCCTCCACC
VK3 (1-236) AGTGGCAGTGGGTCTGGGAC AAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAG
VL]::huKLC
AGAGTTCACTCTCACCATCAG CACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGG
-CL +
CAGCCTGCAGTCTGAAGATTT ACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
[Unknown TGCAGTTTATTACTGTCAGCA GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
anti-NA GTATCAGAACTGGCCTCTCAC GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC
<huGIPR>
TTTCGGCGGAGGGACCAAGGT CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTG
2G10.610 GGAGATCAAACGAACGGTGG AATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTG
VH3 :huIgG1(1-472) CTGCACCATCTGTCTTCATCTT AGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGC
VH]:

CCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTC

z GAAATCTGGAACTGCCTCTGT CCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCC
(mAb); LMR
TGTGTGCCTGCTGAATAACTT TGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACC
ID: 26228 SS-CTATCCCAGAGAGGCCAAAG CTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTG
TACAGTGGAAGGTGGATAAC CATAATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCA

GCCCTCCAATCGGGTAACTCC GCACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAG
re) CAGGAGAGTGTCACAGAGCA GACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCA
`z. GGACAGCAAGGACAGCACCT
ACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAA
oe ACAGCCTCAGCAGCACCCTGA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCC
CGCTGAGCAAAGCAGACTAC CCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTG
oe oe GAGAAACACAAAGTCTACGC ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGT
CTGCGAAGTCACCCATCAGGG GGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAG
CCTGAGCTCGCCCGTCACAAA ACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTC
GAGCTTCAACAGGGGAGAGT TATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGG
GT
GGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCAC
AACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAA
A
(SEQ ID NO: 40) (SEQ ID NO: 41) EIVMTQSPATL SVSPGERATLS QVQLVE SGGGVVQPGRSLRL SCAASGFTFSNYGMHWVRQAP
CRASQSVDRHLAWYQQKPGQ GEGLEWVAAIWFDASDKYYADAVKGRFTISRDNSKNTLYLQ
APRLLIYEAATRATGIPARVSGS MNSLRAEDTAVYYCARDLAIFGVVPDYWGQGTLVTVSSASTK
GS GTEFTLTI S SLQ SEDFAVYYC GP SVFPL AP S SKST S GGTAALGCLVKDYFPEPVTVSWN S
GALT
QQYQNWPLTFGGGTKVEIKRT SGVHTFPAVLQSSGLY SLSSVVTVP SSSLGTQTYICNVNHKP SN
VAAPSVFIFPPSDEQLKSGTASV TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
AA
VCLLNNFYPREAKVQWKVDN MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCE
ALQSGNSQESVTEQDSKDSTYS EQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
L SSTLTL SKADYEKHKVYACE SKAKGQPREPQVYTLPP SREEMTKNQVSLTCLVKGFYP SDIAV
VTHQGLSSPVTKSFNRGEC
EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN
VFSCSVMHEALHNHYTQKSLSLSPGK
(SEQ ID NO: 42) (SEQ ID NO: 43) [hu anti- GAAATAGTGATGACGCAGTCT
CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
<huGIPR> CCAGCCACCCTGTCTGTGTCT
TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGGATTCA
2G10.318 CCAGGGGAAAGAGCCACCCT
CCTTCAGTAACTATGGCATGCACTGGGTCCGCCAGGCTCCA
VK3 (1-236) CTCCTGCAGGGCCAGTCAGAG
GGCGAGGGGCTGGAGTGGGTGGCAGCTATATGGTTTGATGC
VL]::huKLC TGTTCTGAGTCACTTAGCCTG
AAGTGATAAATACTATGCAGACGCCGTGAAGGGCCGATTCA
-CL + GTACCAGCAGAAACCTGGCC
CCATCTCCAGAGACAACTCCAAGAACACGCTGTATCTGCAA
[Unknown AGGCTCCCAGGCTCCTCATCT
ATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTG
anti- A N ACGAAGCAGCCACCAGGGCC
TGCGAGAGATTTGGCGATTTTTGGAGTGGTCCCCGACTACT
<huGIPR> ACTGGTATCCCAGCCAGGTTC
GGGGCCAGGGAACCCTGGTCACCGTGTCTAGTGCCTCCACC
2G10.610 AGTGGCAGTGGGTCTGGGAC
AAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAG
VH3 (1-472) AGAGTTCACTCTCACCATCAG

VH]::huIgG1 CAGCCTGCAGTCTGAAGATTT
ACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
oe zSEFL2-2 TGCAGTTTATTACTGTCAGCA
GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
(mAb); LMR GTATAACAACTGGCCTCTCAC
GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC
ID: SS- TTTCGGCGGAGGGACCAAGGT
CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTG

AATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTG oe oe CTGCACCATCTGTCTTCATCTT AGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGC
CCCGCCATCTGATGAGCAGTT CCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTC
GAAATCTGGAACTGCCTCTGT CCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCC
TGTGTGCCTGCTGAATAACTT TGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACC
CTATCCCAGAGAGGCCAAAG CTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTG
TACAGTGGAAGGTGGATAAC CATAATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCA
GCCCTCCAATCGGGTAACTCC GCACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAG
CAGGAGAGTGTCACAGAGCA GACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCA
GGACAGCAAGGACAGCACCT ACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAA
ACAGCCTCAGCAGCACCCTGA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCC
CGCTGAGCAAAGCAGACTAC CCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTG
GAGAAACACAAAGTCTACGC ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGT
CTGCGAAGTCACCCATCAGGG GGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAG
CCTGAGCTCGCCCGTCACAAA ACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTC
GAGCTTCAACAGGGGAGAGT TATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGG
GT
GGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCAC
AACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAA
A
(SEQ ID NO: 44) (SEQ ID NO: 45) EIVMTQSPATLSVSPGERATLS QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMHWVRQAP
CRASQSVLSHLAWYQQKPGQA GEGLEWVAAIWFDASDKYYADAVKGRFTISRDNSKNTLYLQ
PRLLIYEAATRATGIPARFSGSG MNSLRAEDTAVYYCARDLAIFGVVPDYWGQGTLVTVSSASTK
SGTEFTLTISSLQSEDFAVYYCQ GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALT
QYNNWPLTFGGGTKVEIKRTV SGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN
AA AAPSVFIFPPSDEQLKSGTASVV TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
CLLNNFYPREAKVQWKVDNAL MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCE
QSGNSQESVTEQDSKDSTYSLS EQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
STLTLSKADYEKHKVYACEVT SKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAV
HQGLSSPVTKSFNRGEC
EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN
VFSCSVMHEALHNHYTQKSLSLSPGK
(SEQ ID NO: 46) (SEQ ID NO: 47) [hu anti- GAAATAGTGATGACGCAGTCT
CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
<huGIPR> CCAGCCACCCTGTCTGTGTCT
TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGGATTCA
re) 2G10.324 NA CCAGGGGAAAGAGCCACCCT
CCTTCAGTAACTATGGCATGCACTGGGTCCGCCAGGCTCCA
VK3 (1-236) CTCCTGCAGGGCCAGTCAGAG
GGCGAGGGGCTGGAGTGGGTGGCAGCTATATGGTTTGATGC
VL]::huKLC TGTTCTGAGTCACTTAGCCTG
AAGTGATAAATACTATGCAGACGCCGTGAAGGGCCGATTCA oe oe -CL + GTACCAGCAGAAACCTGGCC
CCATCTCCAGAGACAACTCCAAGAACACGCTGTATCTGCAA
[Unknown AGGCTCCCAGGCTCCTCATCT
ATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTG
anti- ACGAAGCAGCCACCAGGGCC
TGCGAGAGATTTGGCGATTTTTGGAGTGGTCCCCGACTACT
<huGIPR> ACTGGTATCCCAGCCAGGTTC
GGGGCCAGGGAACCCTGGTCACCGTGTCTAGTGCCTCCACC
2G10.610 AGTGGCAGTGGGTCTGGGAC
AAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAG
VH3 (1-472) AGAGTTCACTCTCACCATCAG
CACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGG
VH]::huIgG1 CAGCCTGCAGTCTGAAGATTT
ACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
zSEFL2-2 TGCAGTTTATTACTGTCAGCA
GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
(mAb); LMR GTATCAGAACTGGCCTCTCAC
GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC
ID: SS- TTTCGGCGGAGGGACCAAGGT
CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTG

AATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTG
CTGCACCATCTGTCTTCATCTT AGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGC
CCCGCCATCTGATGAGCAGTT CCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTC
GAAATCTGGAACTGCCTCTGT CCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCC
TGTGTGCCTGCTGAATAACTT TGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACC
CTATCCCAGAGAGGCCAAAG CTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTG
TACAGTGGAAGGTGGATAAC CATAATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCA
GCCCTCCAATCGGGTAACTCC GCACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAG
CAGGAGAGTGTCACAGAGCA GACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCA
GGACAGCAAGGACAGCACCT ACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAA
ACAGCCTCAGCAGCACCCTGA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCC
CGCTGAGCAAAGCAGACTAC CCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTG
GAGAAACACAAAGTCTACGC ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGT
CTGCGAAGTCACCCATCAGGG GGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAG
CCTGAGCTCGCCCGTCACAAA ACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTC
GAGCTTCAACAGGGGAGAGT TATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGG
GT
GGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCAC
AACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAA
A
(SEQ ID NO: 48) (SEQ ID NO: 49) EIVMTQSPATLSVSPGERATLS QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMHWVRQAP

CRASQSVLSHLAWYQQKPGQA GEGLEWVAAIWFDASDKYYADAVKGRFTISRDNSKNTLYLQ
AA PRLLIYEAATRATGIPARFSGSG MNSLRAEDTAVYYCARDLAIFGVVPDYWGQGTLVTVSSASTK
SGTEFTLTISSLQSEDFAVYYCQ GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALT
oe QYQNWPLTFGGGTKVEIKRTV SGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN
AAPSVFIFPPSDEQLKSGTASVV TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
oe oe CLLNNFYPREAKVQWKVDNAL MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCE
QSGNSQESVTEQDSKDSTYSLS EQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
STLTLSKADYEKHKVYACEVT SKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAV
HQGLSSPVTKSFNRGEC
EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN
VFSCSVMHEALHNHYTQKSLSLSPGK
(SEQ ID NO: 50) (SEQ ID NO: 51) GAAATAGTGATGACGCAGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
CCAGCCACCCTGTCTGTGTCT TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGGATTCA
CCAGGGGAAAGAGCCACCCT CCTTCAGTAACTATGGCATGCACTGGGTCCGCCAGGCTCCA
CTCCTGCAGGGCCAGTCAGAG GGCGAGGGGCTGGAGTGGGTGGCAGCTATATGGTTTGATGC
TGTTATGAGTCACTTAGCCTG AAGTGATAAATACTATGCAGACGCCGTGAAGGGCCGATTCA
GTACCAGCAGAAACCTGGCC CCATCTCCAGAGACAACTCCAAGAACACGCTGTATCTGCAA
AGGCTCCCAGGCTCCTCATCT ATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTG
[hu anti- ACGAAGCAGCCACCAGGGCC
TGCGAGAGATTTGGCGATTTTTGGAGTGGTCCCCGACTACT
<huGIPR> ACTGGTATCCCAGCCAGGTTC
GGGGCCAGGGAACCCTGGTCACCGTGTCTAGTGCCTCCACC
2G10.322 AGTGGCAGTGGGTCTGGGAC
AAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAG
VK3 (1-236) AGAGTTCACTCTCACCATCAG
CACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGG
VL]::huKLC CAGCCTGCAGTCTGAAGATTT
ACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
-CL + TGCAGTTTATTACTGTCAGCA
GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
[Unknown GTATCAGAACTGGCCTCTCAC
GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC
anti- TTTCGGCGGAGGGACCAAGGT
CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTG
NA
<huGIPR> GGAGATCAAACGAACGGTGG
AATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTG
2G10.610 CTGCACCATCTGTCTTCATCTT
AGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGC
VH3 (1-472) CCCGCCATCTGATGAGCAGTT
CCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTC
VH]::huIgG1 GAAATCTGGAACTGCCTCTGT
CCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCC
zSEFL2-2 TGTGTGCCTGCTGAATAACTT
TGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACC
(mAb); LMR CTATCCCAGAGAGGCCAAAG
CTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTG
ID: SS- TACAGTGGAAGGTGGATAAC
CATAATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCA

GCACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAG
CAGGAGAGTGTCACAGAGCA GACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCA
GGACAGCAAGGACAGCACCT ACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAA

ACAGCCTCAGCAGCACCCTGA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCC
CGCTGAGCAAAGCAGACTAC CCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTG
GAGAAACACAAAGTCTACGC ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGT
oe CTGCGAAGTCACCCATCAGGG GGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAG
CCTGAGCTCGCCCGTCACAAA ACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTC
oe oe GAGCTTCAACAGGGGAGAGT TATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGG
GT
GGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCAC
AACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAA
A
(SEQ ID NO: 52) (SEQ ID NO: 53) oe EIVMTQSPATL SVSPGERATLS QVQLVE SGGGVVQPGRSLRL SCAASGFTFSNYGMHWVRQAP
CRASQSVMSHLAWYQQKPGQ GEGLEWVAAIWFDASDKYYADAVKGRFTISRDNSKNTLYLQ
APRLLIYEAATRATGIPARFSGS MNSLRAEDTAVYYCARDLAIFGVVPDYWGQGTLVTVSSASTK
GS GTEFTLTI S SLQ SEDFAVYYC GP SVFPLAP S SKST S GGTAALGCLVKDYFPEPVTVSWN S GALT
QQYQNWPLTFGGGTKVEIKRT SGVHTFPAVLQSSGLY SLSSVVTVP SSSLGTQTYICNVNHKP SN
VAAPSVFIFPPSDEQLKSGTASV TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
AA
VCLLNNFYPREAKVQWKVDN MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCE
ALQSGNSQESVTEQD SKD STY S EQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
L SSTLTL SKADYEKHKVYACE SKAKGQPREPQVYTLPP SREEMTKNQVSLTCLVKGFYP SDIAV
VTHQGLSSPVTKSFNRGEC EWE SNGQPENNYKTTPPVLD SD
GSFFLY SKLTVD KSRWQQ GN
VFSCSVMHEALHNHYTQKSLSLSPGK
(SEQ ID NO: 54) (SEQ ID NO: 55) GAAATAGTGATGACGCAGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
CCAGCCACCCTGTCTGTGTCT TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGGATTCA
[hu anti-CCAGGGGAAAGAGCCACCCT CCTTCAGTAACTATGGCATGCACTGGGTCCGCCAGGCTCCA
<huGIPR>
CTCCTGCAGGGCCAGTCAGAG GGCGAGGGGCTGGAGTGGGTGGCAGCTATATGGTTTGATGC
2G10.306 TGTTCTGACGCACTTAGCCTG AAGTGATAAATACTATGCAGACGCCGTGAAGGGCCGATTCA
VK3 (1-236) GTACCAGCAGAAACCTGGCC CCATCTCCAGAGACAACTCCAAGAACACGCTGTATCTGCAA
VL]::huKLC
AGGCTCCCAGGCTCCTCATCT ATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTG
-CL +
ACGAAGCAGCCACCAGGGCC TGCGAGAGATTTGGCGATTTTTGGAGTGGTCCCCGACTACT
[Unknown ACTGGTATCCCAGCCAGGTTC GGGGCCAGGGAACCCTGGTCACCGTGTCTAGTGCCTCCACC
anti-NA AGTGGCAGTGGGTCTGGGAC AAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAG
<huGIPR>
AGAGTTCACTCTCACCATCAG CACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGG
2G10.610 CAGCCTGCAGTCTGAAGATTT ACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
VH3 (1-472) VH huI TGCAGTTTATTACTGTCAGCA
GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
]::gG1 SEF GTATCAGAACTGGCCTCTCAC

zL2-2 TTTCGGCGGAGGGACCAAGGT CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTG
(mAb); LMR
GGAGATCAAACGAACGGTGG AATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTG
ID. SS-. = CTGCACCATCTGTCTTCATCTT
AGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGC
oe CCCGCCATCTGATGAGCAGTT CCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTC
GAAATCTGGAACTGCCTCTGT CCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCC
oe oe TGTGTGCCTGCTGAATAACTT TGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACC
CTATCCCAGAGAGGCCAAAG CTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTG
TACAGTGGAAGGTGGATAAC CATAATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCA
GCCCTCCAATCGGGTAACTCC GCACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAG
CAGGAGAGTGTCACAGAGCA GACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCA
GGACAGCAAGGACAGCACCT ACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAA
ACAGCCTCAGCAGCACCCTGA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCC
CGCTGAGCAAAGCAGACTAC CCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTG
GAGAAACACAAAGTCTACGC ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGT
CTGCGAAGTCACCCATCAGGG GGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAG
CCTGAGCTCGCCCGTCACAAA ACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTC
GAGCTTCAACAGGGGAGAGT TATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGG
GT
GGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCAC
AACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAA
A
(SEQ ID NO: 56) (SEQ ID NO: 57) EIVMTQSPATL SVSPGERATLS QVQLVE SGGGVVQPGRSLRL SCAASGFTFSNYGMHWVRQAP
CRASQSVLTHLAWYQQKPGQA GEGLEWVAAIWFDASDKYYADAVKGRFTISRDNSKNTLYLQ
PRLLIYEAATRATGIPARFSGSG MNSLRAEDTAVYYCARDLAIFGVVPDYWGQGTLVTVSSASTK
SGTEFTLTISSLQSEDFAVYYCQ GP SVFPLAP S SKST S GGTAALGCLVKDYFPEPVTVSWN S GALT
QYQNWPLTFGGGTKVEIKRTV SGVHTFPAVLQSSGLY SLSSVVTVP SSSLGTQTYICNVNHKP SN
AA AAP SVFIFPP SDEQLKSGTASVV
TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
CLLNNFYPREAKVQWKVDNAL MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCE
QSGNSQESVTEQD SKD STY SL S EQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
STLTLSKADYEKHKVYACEVT SKAKGQPREPQVYTLPP SREEMTKNQVSLTCLVKGFYP SDIAV
HQGL SSPVTKSFNRGEC EWE SNGQPENNYKTTPPVLD SD
GSFFLY SKLTVD KSRWQQ GN
VFSCSVMHEALHNHYTQKSLSLSPGK
(SEQ ID NO: 58) (SEQ ID NO: 59) [hu anti- GAAATAGTGATGACGCAGTCT
CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
<huGIPR> CCAGCCACCCTGTCTGTGTCT
TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGGATTCA
2G10.331 CCAGGGGAAAGAGCCACCCT

VK3 (1-236) NA CTCCTGCAGGGCCAGTCAGAG GGCGAGGGGCTGGAGTGGGTGGCAGCTATATGGTTTGATGC
VL]::huKLC TGTTGATCTGCACTTAGCCTG
AAGTGATAAATACTATGCAGACGCCGTGAAGGGCCGATTCA
-CL + GTACCAGCAGAAACCTGGCC
CCATCTCCAGAGACAACTCCAAGAACACGCTGTATCTGCAA
oe [Unknown AGGCTCCCAGGCTCCTCATCT
ATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTG
" anti- ACGAAGCAGCCACCAGGGCC
TGCGAGAGATTTGGCGATTTTTGGAGTGGTCCCCGACTACT oe oe <huGIPR> ACTGGTATCCCAGCCAGGTTC
GGGGCCAGGGAACCCTGGTCACCGTGTCTAGTGCCTCCACC
2G10.610 AGTGGCAGTGGGTCTGGGAC
AAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAG
VH3 (1-472) AGAGTTCACTCTCACCATCAG
CACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGG
VH]::huIgG1 CAGCCTGCAGTCTGAAGATTT
ACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
zSEFL2-2 TGCAGTTTATTACTGTCAGCA
GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
(mAb); LMR GTATCAGAACTGGCCTCTCAC
GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC
ID: SS- TTTCGGCGGAGGGACCAAGGT
CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTG

AATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTG
CTGCACCATCTGTCTTCATCTT AGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGC
CCCGCCATCTGATGAGCAGTT CCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTC
GAAATCTGGAACTGCCTCTGT CCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCC
TGTGTGCCTGCTGAATAACTT TGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACC
CTATCCCAGAGAGGCCAAAG CTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTG
TACAGTGGAAGGTGGATAAC CATAATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCA
GCCCTCCAATCGGGTAACTCC GCACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAG
CAGGAGAGTGTCACAGAGCA GACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCA
GGACAGCAAGGACAGCACCT ACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAA
ACAGCCTCAGCAGCACCCTGA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCC
CGCTGAGCAAAGCAGACTAC CCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTG
GAGAAACACAAAGTCTACGC ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGT
CTGCGAAGTCACCCATCAGGG GGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAG
CCTGAGCTCGCCCGTCACAAA ACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTC
GAGCTTCAACAGGGGAGAGT TATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGG
GT
GGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCAC
AACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAA
A
(SEQ ID NO: 60) (SEQ ID NO: 61) EIVMTQ SP ATL SVSPGERATLS QVQLVE SGGGVVQPGRSLRL SCAA S GFTF SNYGMHWVRQ AP
CRASQSVDLHLAWYQQKPGQ GEGLEWVAAIWFDASDKYYADAVKGRFTISRDNSKNTLYLQ
APRLLIYEAATRATGIPARFSGS MNSLRAEDTAVYYCARDLAIFGVVPDYWGQGTLVTVSSASTK
GS GTEFTL TI S SLQSEDFAVYYC GP SVFPL AP S SKST S GGT AALGCL VKDYFPEPVTVSWN S
GAL T

AA QQYQNWPLTFGGGTKVEIKRT SGVHTFPAVLQS SGLY SLS SVVTVP S S
SLGTQTYICNVNHKP SN
VAAPSVFIFPPSDEQLKSGTASV TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
VCLLNNFYPREAKVQWKVDN MI SRTPEVTCVVVDVSHEDPEVKFNWYVD GVEVHNAKTKPCE
oe ALQSGNSQESVTEQD SKD STY S EQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
L SSTLTL SKADYEKHKVYACE SKAKGQPREPQVYTLPP SREEMTKNQVSLTCLVKGFYP SDIAV
oe oe VTHQGLSSPVTKSFNRGEC
EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN
VFSCSVMHEALHNHYTQKSLSLSPGK
(SEQ ID NO: 62) (SEQ ID NO: 63) GAAATAGTGATGACGCAGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
CCAGCCACCCTGTCTGTGTCT TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGGATTCA
oe CCAGGGGAAAGAGCCACCCT CCTTCAGTAACTATGGCATGCACTGGGTCCGCCAGGCTCCA
CTCCTGCAGGGCCAGTCAGAG GGCGAGGGGCTGGAGTGGGTGGCAGCTATATGGTTTGATGC
TGTTAGCGAACACTTAGCCTG AAGTGATAAATACTATGCAGACGCCGTGAAGGGCCGATTCA
GTACCAGCAGAAACCTGGCC CCATCTCCAGAGACAACTCCAAGAACACGCTGTATCTGCAA
AGGCTCCCAGGCTCCTCATCT ATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTG
ACGAAGCAGCCACCAGGGCC TGCGAGAGATCTGGCGATTTTTGGAGTGATTCCCGACTACT
ACTGGTATCCCAGCCAGGTTC GGGGCCAGGGAACCCTGGTCACCGTGTCTAGTGCCTCCACC
[hu anti- AGTGGCAGTGGGTCTGGGAC
AAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAG
<huGIPR> AGAGTTCACTCTCACCATCAG
CACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGG
2G10.320 CAGCCTGCAGTCTGAAGATTT
ACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
VK3 (1-236) TGCAGTTTATTACTGTCAGCA
GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA p VL]::huKLC GTATCAGAACTGGCCTCTCAC
GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC
-CL + [hu TTTCGGCGGAGGGACCAAGGT
CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTG
anti- GGAGATCAAACGAACGGTGG
AATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTG
<huGIPR> NA CTGCACCATCTGTCTTCATCTT
AGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGC
2G10.320 CCCGCCATCTGATGAGCAGTT
CCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTC
VH3 (1-472) GAAATCTGGAACTGCCTCTGT
CCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCC
VH]::huIgG1 TGTGTGCCTGCTGAATAACTT
TGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACC
zSEFL2-2 CTATCCCAGAGAGGCCAAAG
CTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTG
(mAb); LMR TACAGTGGAAGGTGGATAAC
CATAATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCA
ID: SS- GCCCTCCAATCGGGTAACTCC
GCACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAG

GACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCA
GGACAGCAAGGACAGCACCT ACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAA
ACAGCCTCAGCAGCACCCTGA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCC
CGCTGAGCAAAGCAGACTAC CCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTG
GAGAAACACAAAGTCTACGC ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGT

CTGCGAAGTCACCCATCAGGG GGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAG
CCTGAGCTCGCCCGTCACAAA ACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTC
GAGCTTCAACAGGGGAGAGT TATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGG
oe GT
GGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCAC
AACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAA
oe cr oe A
(SEQ ID NO: 64) (SEQ ID NO: 65) EIVMTQSPATLSVSPGERATLS QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMHWVRQAP

n.) CRASQSVSEHLAWYQQKPGQA GEGLEWVAAIWFDASDKYYADAVKGRFTISRDNSKNTLYLQ
=
PRLLIYEAATRATGIPARFSGSG MNSLRAEDTAVYYCARDLAIFGVIPDYWGQGTLVTVSSASTK
oe i-J
SGTEFTLTISSLQSEDFAVYYCQ GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALT
c,.) --.1 QYQNWPLTFGGGTKVEIKRTV SGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN
o AA AAPSVFIFPPSDEQLKSGTASVV TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
--.1 CLLNNFYPREAKVQWKVDNAL MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCE
QSGNSQESVTEQDSKDSTYSLS EQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
STLTLSKADYEKHKVYACEVT SKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAV
HQGLSSPVTKSFNRGEC
EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN
VFSCSVMHEALHNHYTQKSLSLSPGK
(SEQ ID NO: 66) (SEQ ID NO: 67) GAAATAGTGATGACGCAGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
CCAGCCACCCTGTCTGTGTCT TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGGATTCA
p CCAGGGGAAAGAGCCACCCT CCTTCAGTAACTATGGCATGCACTGGGTCCGCCAGGCTCCA
[hu anti- CTCCTGCAGGGCCAGTCAGAG
GGCGAGGGGCTGGAGTGGGTGGCAGCTATATGGTTTGATGC .
, <huGIPR> TGTTAGCGAACACTTAGCCTG
AAGTGATAAATACTATGCAGACGCCGTGAAGGGCCGATTCA .
2G10.320 GTACCAGCAGAAACCTGGCC
CCATCTCCAGAGACAACTCCAAGAACACGCTGTATCTGCAA
, VK3 (1-236) AGGCTCCCAGGCTCCTCATCT
ATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTG .
, , VL]::huKLC ACGAAGCAGCCACCAGGGCC
TGCGAGAGATTTGGCGATTTTTGGAGTGGTCCCCGACTACT .
, -CL + ACTGGTATCCCAGCCAGGTTC
GGGGCCAGGGAACCCTGGTCACCGTGTCTAGTGCCTCCACC , [Unknown AGTGGCAGTGGGTCTGGGAC
AAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAG
anti- NA AGAGTTCACTCTCACCATCAG
CACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGG
<huGIPR> CAGCCTGCAGTCTGAAGATTT
ACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
2G10.610 TGCAGTTTATTACTGTCAGCA
GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
VH3 (1-472) GTATCAGAACTGGCCTCTCAC
GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC
VH]::huIgG1 TTTCGGCGGAGGGACCAAGGT
CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTG
z5EFL2-2 GGAGATCAAACGAACGGTGG

n (mAb); LMR CTGCACCATCTGTCTTCATCTT

ID: SS- CCCGCCATCTGATGAGCAGTT
CCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTC
cp CCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCC n.) n o o TGTGTGCCTGCTGAATAACTT
TGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACC
oe Pi CTATCCCAGAGAGGCCAAAG
CTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTG 'a TACAGTGGAAGGTGGATAAC CATAATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCA
oe cr oe GCCCTCCAATCGGGTAACTCC GCACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAG
CAGGAGAGTGTCACAGAGCA GACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCA
GGACAGCAAGGACAGCACCT ACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAA
ACAGCCTCAGCAGCACCCTGA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCC
CGCTGAGCAAAGCAGACTAC CCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTG
GAGAAACACAAAGTCTACGC ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGT
CTGCGAAGTCACCCATCAGGG GGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAG
CCTGAGCTCGCCCGTCACAAA ACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTC
GAGCTTCAACAGGGGAGAGT TATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGG
GT
GGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCAC
AACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAA
A
(SEQ ID NO: 68) (SEQ ID NO: 69) EIVMTQSPATLSVSPGERATLS QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMHWVRQAP
CRASQSVSEHLAWYQQKPGQA GEGLEWVAAIWFDASDKYYADAVKGRFTISRDNSKNTLYLQ
PRLLIYEAATRATGIPARFSGSG MNSLRAEDTAVYYCARDLAIFGVVPDYWGQGTLVTVSSASTK
SGTEFTLTISSLQSEDFAVYYCQ GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALT
QYQNWPLTFGGGTKVEIKRTV SGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN
AAPSVFIFPPSDEQLKSGTASVV TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
AA
CLLNNFYPREAKVQWKVDNAL MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCE
QSGNSQESVTEQDSKDSTYSLS EQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
STLTLSKADYEKHKVYACEVT SKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAV
HQGLSSPVTKSFNRGEC
EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN
VFSCSVMHEALHNHYTQKSLSLSPGK
(SEQ ID NO: 70) (SEQ ID NO: 71) [hu anti- GAAATAGTGATGACGCAGTCT
CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
<huGIPR> CCAGCCACCCTGTCTGTGTCT
TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGGATTCA
2G10.333 CCAGGGGAAAGAGCCACCCT
CCTTCAGTAACTATGGCATGCACTGGGTCCGCCAGGCTCCA
VK3 (1-236) CTCCTGCAGGGCCAGTCAGAG
GGCGAGGGGCTGGAGTGGGTGGCAGCTATATGGTTTGATGC
VL]::huKLC TGTTAGCCGGCACTTAGCCTG
AAGTGATAAATACTATGCAGACGCCGTGAAGGGCCGATTCA
-CL + NA GTACCAGCAGAAACCTGGCC

[Unknown AGGCTCCCAGGCTCCTCATCT
ATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTG
re) re) anti- ACGAAGCAGCCACCAGGGCC
TGCGAGAGATTTGGCGATTTTTGGAGTGGTCCCCGACTACT
re) <huGIPR> ACTGGTATCCCAGCCAGGTTC
GGGGCCAGGGAACCCTGGTCACCGTGTCTAGTGCCTCCACC
2G10.610 AGTGGCAGTGGGTCTGGGAC
AAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAG
VH3 (1-472) AGAGTTCACTCTCACCATCAG
CACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGG oe oe VH]::huIgG1 CAGCCTGCAGTCTGAAGATTT
ACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
zSEFL2-2 TGCAGTTTATTACTGTCAGCA
GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
(mAb); LMR GTATCAGCACTGGCCTCTCAC
GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC
ID: SS- TTTCGGCGGAGGGACCAAGGT
CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTG

AATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTG
CTGCACCATCTGTCTTCATCTT AGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGC
CCCGCCATCTGATGAGCAGTT CCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTC
GAAATCTGGAACTGCCTCTGT CCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCC
TGTGTGCCTGCTGAATAACTT TGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACC
CTATCCCAGAGAGGCCAAAG CTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTG
TACAGTGGAAGGTGGATAAC CATAATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCA
GCCCTCCAATCGGGTAACTCC GCACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAG
CAGGAGAGTGTCACAGAGCA GACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCA
GGACAGCAAGGACAGCACCT ACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAA
ACAGCCTCAGCAGCACCCTGA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCC
CGCTGAGCAAAGCAGACTAC CCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTG
GAGAAACACAAAGTCTACGC ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGT
CTGCGAAGTCACCCATCAGGG GGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAG
CCTGAGCTCGCCCGTCACAAA ACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTC
GAGCTTCAACAGGGGAGAGT TATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGG
GT
GGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCAC
AACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAA
A
(SEQ ID NO: 72) (SEQ ID NO: 73) EIVMTQSPATLSVSPGERATLS QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMHWVRQAP
CRASQSVSRHLAWYQQKPGQA GEGLEWVAAIWFDASDKYYADAVKGRFTISRDNSKNTLYLQ
PRLLIYEAATRATGIPARFSGSG MNSLRAEDTAVYYCARDLAIFGVVPDYWGQGTLVTVSSASTK
SGTEFTLTISSLQSEDFAVYYCQ GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALT
QYQHWPLTFGGGTKVEIKRTV SGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN
AA AAPSVFIFPPSDEQLKSGTASVV TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
CLLNNFYPREAKVQWKVDNAL MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCE

QSGNSQESVTEQDSKDSTYSLS EQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
STLTLSKADYEKHKVYACEVT SKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAV
HQGLSSPVTKSFNRGEC
EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN
oe VFSCSVMHEALHNHYTQKSLSLSPGK
(SEQ ID NO: 74) (SEQ ID NO: 75) oe oe GAAATAGTGATGACGCAGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
CCAGCCACCCTGTCTGTGTCT TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGGATTCA
CCAGGGGAAAGAGCCACCCT CCTTCCAGAACTATGGCATGCACTGGGTCCGCCAGGCTCCA

CTCCTGCAGGGCCAGTCAGAG GGCGAGGGGCTGGAGTGGGTGGCAGCTATATGGTTTGATGC
o TGTTTTCAGCCACTTAGCCTG GTCTGACAAATACTATGCAGACGCCGTGAAGGGCCGATTCA
oe GTACCAGCAGAAACCTGGCC CCATCTCCAGAGACAACTCCAAGAACACGCTGTATCTGCAA
c,.) AGGCTCCCAGGCTCCTCATCT ATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTG
o vo ACGAAGCAGCCACCAGGGCC TGCGAGAGATCTTGCGATTTTTGGAGTGGTCCCCGACTACTG

ACTGGTATCCCAGCCAGGTTC GGGCCAGGGAACCCTGGTCACCGTGTCTAGTGCCTCCACCA
AGTGGCAGTGGGTCTGGGAC AGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGC
AGAGTTCACTCTCACCATCAG ACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGA
[hu anti-CAGCCTGCAGTCTGAAGATTT CTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCG
<huGIPR>
TGCAGTTTATTACTGTCAGCA CCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAG
2G10.301 GTATCAGAACTGGCCTCTCAC TCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCC
VK3 (1-236) TTTCGGCGGAGGGACCAAGGT TCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAA
VL]::huKLC
GGAGATCAAACGAACGGTGG TCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAG
P
-CL + [hu CTGCACCATCTGTCTTCATCTT CCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCC
o anti- NA
,D
CCCGCCATCTGATGAGCAGTT AGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCC
.
<huGIPR>
, GAAATCTGGAACTGCCTCTGT CCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTG
"
2G10.301 .
TGTGTGCCTGCTGAATAACTT AGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCT
"
,D
VH3 (1-472) , CTATCCCAGAGAGGCCAAAG GAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCA
' , VH]::huIgG1 , TACAGTGGAAGGTGGATAAC TAATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCAGC
, zSEFL2-2 GCCCTCCAATCGGGTAACTCC ACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAGGA
, (mAb); LMR
CAGGAGAGTGTCACAGAGCA CTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCAACA
ID: SS-GGACAGCAAGGACAGCACCT AAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCC

ACAGCCTCAGCAGCACCCTGA AAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCC
CGCTGAGCAAAGCAGACTAC ATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCT
GAGAAACACAAAGTCTACGC GCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAG
CTGCGAAGTCACCCATCAGGG TGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCA
CCTGAGCTCGCCCGTCACAAA CGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATA

GAGCTTCAACAGGGGAGAGT GCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAA
n GT
CGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCA
,-CTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA ___________________________ cp o n o o (SEQ ID NO: 76) (SEQ ID NO:
77) oe Pi AA EIVMTQSPATLSVSPGERATLS

CRASQSVFSHLAWYQQKPGQA GEGLEWVAAIWFDASDKYYADAVKGRFTISRDNSKNTLYLQ
oe c:
oe PRLLIYEAATRATGIPARFSGSG MNSLRAEDTAVYYCARDLAIFGVVPDYWGQGTLVTVSSASTK
SGTEFTLTISSLQSEDFAVYYCQ GP SVFPL AP S SKST S GGTAALGCLVKDYFPEPVTVSWN S GAL T
QYQNWPLTFGGGTKVEIKRTV SGVHTFPAVLQSSGLY SLSSVVTVP SSSLGTQTYICNVNHKP SN
AAP SVFIFPP SDEQLKSGTASVV TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
CLLNNFYPREAKVQWKVDNAL MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCE
QSGNSQESVTEQD SKD STY SL S EQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
STLTLSKADYEKHKVYACEVT SKAKGQPREPQVYTLPP SREEMTKNQVSLTCLVKGFYP SDIAV
HQGL SSPVTKSFNRGEC
EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN
VFSCSVMHEALHNHYTQKSLSLSPGK
(SEQ ID NO: 78) (SEQ ID NO: 79) GAAATAGTGATGACGCAGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
CCAGCCACCCTGTCTGTGTCT TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGGATTCA
CCAGGGGAAAGAGCCACCCT CCTTCCAGAACTATGGCATGCACTGGGTCCGCCAGGCTCCA
CTCCTGCAGGGCCAGTCAGAG GGCGAGGGGCTGGAGTGGGTGGCAGCTATATGGTTTGATGC
TGTTTTCAGCCACTTAGCCTG GTCTGACAAATACTATGCAGACGCCGTGAAGGGCCGATTCA
GTACCAGCAGAAACCTGGCC CCATCTCCAGAGACAACTCCAAGAACACGCTGTATCTGCAA
[hu anti-AGGCTCCCAGGCTCCTCATCT ATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTG
<huGIPR>
ACGAAGCAGCCACCAGGGCC TGCGAGAGATCTTGCGATTTTTGGAGTGGTCCCCGACTACTG
2G10.601 ACTGGTATCCCAGCCAGGGTC GGGCCAGGGAACCCTGGTCACCGTGTCTAGTGCCTCCACCA
VK3 (1-236) AGTGGCAGTGGGTCTGGGAC AGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGC
VL]::huKLC
AGAGTTCACTCTCACCATCAG ACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGA
-CL + [hu CAGCCTGCAGTCTGAAGATTT CTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCG
anti-TGCAGTTTATTACTGTCAGCA CCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAG
<huGIPR> NA
GTATCAGAACTGGCCTCTCAC TCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCC
2G10.301 VH3 1472) TTTCGGCGGAGGGACCAAGGT TCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAA
( VH GGAGATCAAACGAACGGTGG
TCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAG
] mIgG1 ::I
CTGCACCATCTGTCTTCATCTT CCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCC
zSEFL2-2 CCCGCCATCTGATGAGCAGTT AGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCC
(mAb); LMR
GAAATCTGGAACTGCCTCTGT CCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTG
ID: 26226 SS-TGTGTGCCTGCTGAATAACTT AGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCT
CTATCCCAGAGAGGCCAAAG GAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCA

TACAGTGGAAGGTGGATAAC TAATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCAGC
GCCCTCCAATCGGGTAACTCC ACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAGGA
`z. CAGGAGAGTGTCACAGAGCA
CTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCAACA
oe GGACAGCAAGGACAGCACCT AAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCC
ACAGCCTCAGCAGCACCCTGA AAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCC
oe oe CGCTGAGCAAAGCAGACTAC ATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCT
GAGAAACACAAAGTCTACGC GCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAG
CTGCGAAGTCACCCATCAGGG TGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCA
CCTGAGCTCGCCCGTCACAAA CGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATA
GAGCTTCAACAGGGGAGAGT GCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAA
GT
CGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCA
CTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA
(SEQ ID NO: 80) (SEQ ID NO: 81) EIVMTQ SP ATL SVSPGERATLS QVQLVE SGGGVVQPGRSLRL SCAASGFTFQNYGMHWVRQAP
CRASQSVFSHLAWYQQKPGQA GEGLEWVAAIWFDASDKYYADAVKGRFTISRDNSKNTLYLQ
PRLLIYEAATRATGIPARVSGSG MNSLRAEDTAVYYCARDLAIFGVVPDYWGQGTLVTVSSASTK
SGTEFTLTISSLQSEDFAVYYCQ GP SVFPL AP S SKST S GGTAALGCLVKDYFPEPVTVSWN S GAL T
QYQNWPLTFGGGTKVEIKRTV SGVHTFPAVLQSSGLY SLSSVVTVP SSSLGTQTYICNVNHKP SN
AAP SVFIFPP SDEQLKSGTASVV TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
AA
CLLNNFYPREAKVQWKVDNAL MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCE
QSGNSQESVTEQD SKD STY SL S EQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
STLTLSKADYEKHKVYACEVT SKAKGQPREPQVYTLPP SREEMTKNQVSLTCLVKGFYP SDIAV
HQGL SSPVTKSFNRGEC
EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN
VFSCSVMHEALHNHYTQKSLSLSPGK
(SEQ ID NO: 82) (SEQ ID NO: 83) h GAAATAGTGATGACGCAGTCT
CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
[u anti-CCAGCCACCCTGTCTGTGTCT TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGGATTCA
<huGIPR>
CCAGGGGAAAGAGCCACCCT CCTTCCAGAACTATGGCATGCACTGGGTCCGCCAGGCTCCA
2G10.326 VK3 1236) CTCCTGCAGGGCCAGTCAGAG GGCGAGGGGCTGGAGTGGGTGGCAGCTATATGGTTTGATGC
(-TGTTCTGAGTCACTTAGCCTG GTCTGACAAATACTATGCAGACGCCGTGAAGGGCCGATTCA
VL]::huKLC
GTACCAGCAGAAACCTGGCC CCATCTCCAGAGACAACTCCAAGAACACGCTGTATCTGCAA
-CL + [hu AGGCTCCCAGGCTCCTCATCT ATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTG
anti-ACGAAGCAGCCACCAGGGCC TGCGAGAGATCTTGCGATTTTTGGAGTGGTCCCCGACTACTG
<huGIPR> NA
ACTGGTATCCCAGCCAGGTTC GGGCCAGGGAACCCTGGTCACCGTGTCTAGTGCCTCCACCA
2G10.301 VH3 1 472) AGTGGCAGTGGGTCTGGGAC AGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGC
( AGAGTTCACTCTCACCATCAG ACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGA

VH]: -:huIgG1 CAGCCTGCAGTCTGAAGATTT CTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCG
zSEFL=2-2 TGCAGTTTATTACTGTCAGCA CCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAG
cr'n! (mAb); LMR
GTATCAGCAGTGGCCTCTCAC TCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCC
It' ID: SS-oe TTTCGGCGGAGGGACCAAGGT TCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAA
==.?1 26203 GGAGATCAAACGAACGGTGG TCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAG
oe oe CTGCACCATCTGTCTTCATCTT CCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCC
CCCGCCATCTGATGAGCAGTT AGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCC
GAAATCTGGAACTGCCTCTGT CCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTG
TGTGTGCCTGCTGAATAACTT AGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCT
CTATCCCAGAGAGGCCAAAG GAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCA
TACAGTGGAAGGTGGATAAC TAATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCAGC
GCCCTCCAATCGGGTAACTCC ACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAGGA
CAGGAGAGTGTCACAGAGCA CTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCAACA
GGACAGCAAGGACAGCACCT AAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCC
ACAGCCTCAGCAGCACCCTGA AAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCC
CGCTGAGCAAAGCAGACTAC ATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCT
GAGAAACACAAAGTCTACGC GCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAG
CTGCGAAGTCACCCATCAGGG TGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCA
CCTGAGCTCGCCCGTCACAAA CGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATA
GAGCTTCAACAGGGGAGAGT GCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAA
GT
CGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCA
CTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA
(SEQ ID NO: 84) (SEQ ID NO: 85) EIVMTQSPATLSVSPGERATLS QVQLVESGGGVVQPGRSLRLSCAASGFTFQNYGMHWVRQAP
CRASQSVLSHLAWYQQKPGQA GEGLEWVAAIWFDASDKYYADAVKGRFTISRDNSKNTLYLQ
PRLLIYEAATRATGIPARFSGSG MNSLRAEDTAVYYCARDLAIFGVVPDYWGQGTLVTVSSASTK
SGTEFTLTISSLQSEDFAVYYCQ GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALT
QYQQWPLTFGGGTKVEIKRTV SGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN
AAPSVFIFPPSDEQLKSGTASVV TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
AA
CLLNNFYPREAKVQWKVDNAL MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCE
QSGNSQESVTEQDSKDSTYSLS EQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
STLTLSKADYEKHKVYACEVT SKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAV
HQGLSSPVTKSFNRGEC
EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN
VFSCSVMHEALHNHYTQKSLSLSPGK
(SEQ ID NO: 86) (SEQ ID NO: 87) [hu anti- GAAATAGTGATGACGCAGTCT

<huGIPR> CCAGCCACCCTGTCTGTGTCT
TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGGATTCA
2G10.308 A CCAGGGGAAAGAGCCACCCT
CCTTCAGTAACTATGGCATGCACTGGGTCCGCCAGGCTCCA
N re) VK3 (1-236) CTCCTGCAGGGCCAGTCAGAG
GGCGAGGGGCTGGAGTGGGTGGCAGCTATATGGTTTGATGC
VL]::huKLC TGTTTTCAGCCACTTAGCCTG
AAGTGATAAATACTATGCAGACGCCGTGAAGGGCCGATTCA
-CL + GTACCAGCAGAAACCTGGCC
CCATCTCCAGAGACAACTCCAAGAACACGCTGTATCTGCAA oe oe [Unknown AGGCTCCCAGGCTCCTCATCT
ATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTG
anti- ACGAAGCAGCCACCAGGGCC
TGCGAGAGATTTGGCGATTTTTGGAGTGGTCCCCGACTACT
<huGIPR> ACTGGTATCCCAGCCAGGTTC
GGGGCCAGGGAACCCTGGTCACCGTGTCTAGTGCCTCCACC
2G10.610 AGTGGCAGTGGGTCTGGGAC
AAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAG
VH3 (1-472) AGAGTTCACTCTCACCATCAG
CACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGG
VH]::huIgG1 CAGCCTGCAGTCTGAAGATTT
ACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
zSEFL2-2 TGCAGTTTATTACTGTCAGCA
GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
(mAb); LMR GTATCAGCAGTGGCCTCTCAC
GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC
ID: SS- TTTCGGCGGAGGGACCAAGGT
CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTG

AATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTG
CTGCACCATCTGTCTTCATCTT AGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGC
CCCGCCATCTGATGAGCAGTT CCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTC
GAAATCTGGAACTGCCTCTGT CCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCC
TGTGTGCCTGCTGAATAACTT TGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACC
CTATCCCAGAGAGGCCAAAG CTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTG
TACAGTGGAAGGTGGATAAC CATAATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCA
GCCCTCCAATCGGGTAACTCC GCACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAG
CAGGAGAGTGTCACAGAGCA GACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCA
GGACAGCAAGGACAGCACCT ACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAA
ACAGCCTCAGCAGCACCCTGA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCC
CGCTGAGCAAAGCAGACTAC CCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTG
GAGAAACACAAAGTCTACGC ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGT
CTGCGAAGTCACCCATCAGGG GGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAG
CCTGAGCTCGCCCGTCACAAA ACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTC
GAGCTTCAACAGGGGAGAGT TATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGG
GT
GGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCAC
AACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAA
A
(SEQ ID NO: 88) (SEQ ID NO: 89) EIVMTQ SP ATL SVSPGERATLS QVQLVE SGGGVVQPGRSLRL SCAA S GFTF SNYGMHWVRQ AP
CRASQSVFSHLAWYQQKPGQA GEGLEWVAAIWFDASDKYYADAVKGRFTISRDNSKNTLYLQ

PRLLIYEAATRATGIPARFSGSG MNSLRAEDTAVYYCARDLAIFGVVPDYWGQGTLVTVSSASTK
AA SGTEFTLTIS SLQSEDFAVYYCQ GP SVFPL AP S SKST S GGT AALGCL
VKDYFPEPVTVSWN S GAL T
QYQQWPLTFGGGTKVEIKRTV SGVHTFPAVLQS SGLY SLS SVVTVP S S SLGTQTYICNVNHKP SN
oe AAP SVFIFPP SDEQLKSGTASVV TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
CLLNNFYPREAKVQWKVDNAL MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCE
oe oe QSGNSQESVTEQDSKDSTYSLS EQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
STLTLSKADYEKHKVYACEVT SKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAV
HQGLSSPVTKSFNRGEC
EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN
VFSCSVMHEALHNHYTQKSLSLSPGK
(SEQ ID NO: 90) (SEQ ID NO: 91) oe GAAATAGTGATGACGCAGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
CCAGCCACCCTGTCTGTGTCT TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGGATTCA
CCAGGGGAAAGAGCCACCCT CCTTCAGTAACTATGGCATGCACTGGGTCCGCCAGGCTCCA
CTCCTGCAGGGCCAGTCAGAG GGCGAGGGGCTGGAGTGGGTGGCAGCTATATGGTTTGATGC
TGTTTTCAGCCACTTAGCCTG AAGTGATAAATACTATGCAGACGCCGTGAAGGGCCGATTCA
GTACCAGCAGAAACCTGGCC CCATCTCCAGAGACAACTCCAAGAACACGCTGTATCTGCAA
AGGCTCCCAGGCTCCTCATCT ATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTG
ACGAAGCAGCCACCAGGGCC TGCGAGAGATTTGGCGATTTTTGGAGTGGTCCCCGACTACT
[hu anti-ACTGGTATCCCAGCCAGGGTC GGGGCCAGGGAACCCTGGTCACCGTGTCTAGTGCCTCCACC
<huGIPR>
AGTGGCAGTGGGTCTGGGAC AAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAG
2G10.608 VK3 1 236) AGAGTTCACTCTCACCATCAG CACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGG
- ( CAGCCTGCAGTCTGAAGATTT ACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
VL]::huKLC
TGCAGTTTATTACTGTCAGCA GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
-CL +
GTATCAGCAGTGGCCTCTCAC GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC
[Unknown TTTCGGCGGAGGGACCAAGGT CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTG
anti-NA GGAGATCAAACGAACGGTGG AATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTG
<huGIPR>
CTGCACCATCTGTCTTCATCTT AGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGC
2G10.610 CCCGCCATCTGATGAGCAGTT CCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTC

::huIgG1 (1-472) GAAATCTGGAACTGCCTCTGT CCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCC
VH]
SEF TGTGTGCCTGCTGAATAACTT
TGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACC
zL2-2 CTATCCCAGAGAGGCCAAAG CTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTG
(mAb); LMR
TACAGTGGAAGGTGGATAAC CATAATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCA
ID: SS-GCCCTCCAATCGGGTAACTCC GCACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAG

CAGGAGAGTGTCACAGAGCA GACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCA
GGACAGCAAGGACAGCACCT ACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAA
ACAGCCTCAGCAGCACCCTGA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCC
CGCTGAGCAAAGCAGACTAC CCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTG
ci) GAGAAACACAAAGTCTACGC ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGT
`z. CTGCGAAGTCACCCATCAGGG
GGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAG
CCTGAGCTCGCCCGTCACAAA ACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTC
GAGCTTCAACAGGGGAGAGT TATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGG
cr GT
GGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCAC
AACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAA
A
(SEQ ID NO: 92) (SEQ ID NO: 93) EIVMTQSPATL SVSPGERATLS QVQLVE SGGGVVQPGRSLRL SCAASGFTFSNYGMHWVRQAP
oe CRASQSVFSHLAWYQQKPGQA GEGLEWVAAIWFDASDKYYADAVKGRFTISRDNSKNTLYLQ
PRLLIYEAATRATGIPARVSGSG MNSLRAEDTAVYYCARDLAIFGVVPDYWGQGTLVTVSSASTK
SGTEFTLTISSLQSEDFAVYYCQ GP SVFPL AP S SKST S GGTAALGCLVKDYFPEPVTVSWN S GAL T
QYQQWPLTFGGGTKVEIKRTV SGVHTFPAVLQSSGLY SLSSVVTVP SSSLGTQTYICNVNHKP SN
AA AAP SVFIFPP SDEQLKSGTASVV
TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
CLLNNFYPREAKVQWKVDNAL MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCE
QSGNSQESVTEQD SKD STY SL S EQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
STLTLSKADYEKHKVYACEVT SKAKGQPREPQVYTLPP SREEMTKNQVSLTCLVKGFYP SDIAV
HQGL SSPVTKSFNRGEC
EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN
VFSCSVMHEALHNHYTQKSLSLSPGK
(SEQ ID NO: 94) (SEQ ID NO: 95) p GAAATAGTGATGACGCAGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
CCAGCCACCCTGTCTGTGTCT TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGGATTCA
CCAGGGGAAAGAGCCACCCT CCTTCAGTAACTATGGCATGCACTGGGTCCGCCAGGCTCCA
[hu anti-GIPR> CTCCTGCAGGGCCAGTCAGAG
GGCGAGGGGCTGGAGTGGGTGGCAGCTATATGGTTTGATGC
<hu TGTTCAGAGCCACTTAGCCTG AAGTGATAAATACTATGCAGACGCCGTGAAGGGCCGATTCA
2G10.336 GTACCAGCAGAAACCTGGCC CCATCTCCAGAGACAACTCCAAGAACACGCTGTATCTGCAA
VK3 (1-236) AGGCTCCCAGGCTCCTCATCT ATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTG
VL]::huKLC
ACGAAGCAGCCACCAGGGCC TGCGAGAGATATTGCGATTTTTGGAGTGGTCCCCGACTACT
-CL + [hu ACTGGTATCCCAGCCAGGTTC GGGGCCAGGGAACCCTGGTCACCGTGTCTAGTGCCTCCACC
NA
anti-AGTGGCAGTGGGTCTGGGAC AAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAG
<huGIPR>
2G10.325 AGAGTTCACTCTCACCATCAG
CACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGG
CAGCCTGCAGTCTGAAGATTT ACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
VH3 (1-472) TGCAGTTTATTACTGTCAGCA GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
VH]::huIgG1 SEF GTATCAGAACTGGCCTCTCAC GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC

z TTTCGGCGGAGGGACCAAGGT CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTG

(m b), LMR
GGAGATCAAACGAACGGTGG AATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTG
,z ID: SS-re) f 1 26213 CTGCACCATCTGTCTTCATCTT AGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGC
CCCGCCATCTGATGAGCAGTT CCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTC
oe GAAATCTGGAACTGCCTCTGT CCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCC
TGTGTGCCTGCTGAATAACTT TGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACC
oe cr oe CTATCCCAGAGAGGCCAAAG CTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTG
TACAGTGGAAGGTGGATAAC CATAATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCA
GCCCTCCAATCGGGTAACTCC GCACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAG
CAGGAGAGTGTCACAGAGCA GACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCA
GGACAGCAAGGACAGCACCT ACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAA
ACAGCCTCAGCAGCACCCTGA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCC
CGCTGAGCAAAGCAGACTAC CCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTG
GAGAAACACAAAGTCTACGC ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGT
CTGCGAAGTCACCCATCAGGG GGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAG
CCTGAGCTCGCCCGTCACAAA ACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTC
GAGCTTCAACAGGGGAGAGT TATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGG
GT
GGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCAC
AACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAA
A
(SEQ ID NO: 96) (SEQ ID NO: 97) EIVMTQSPATL SVSPGERATLS QVQLVE SGGGVVQPGRSLRL SCAASGFTFSNYGMHWVRQAP
CRASQSVQSHLAWYQQKPGQ GEGLEWVAAIWFDASDKYYADAVKGRFTISRDNSKNTLYLQ
APRLLIYEAATRATGIPARFSGS MNSLRAEDTAVYYCARDIAIFGVVPDYWGQGTLVTVSSASTK
GS GTEFTLTI S SLQ SEDFAVYYC GP SVFPLAP S SKST S GGTAALGCLVKDYFPEPVTVSWN S GALT

QQYQNWPLTFGGGTKVEIKRT SGVHTFPAVLQSSGLY SLSSVVTVP SSSLGTQTYICNVNHKP SN
VAAPSVFIFPPSDEQLKSGTASV TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
AA
VCLLNNFYPREAKVQWKVDN MI SRTPEVTCVVVDVSHEDPEVKFNWYVD GVEVHNAKTKPCE
ALQSGNSQESVTEQD SKD STY S EQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
L SSTLTL SKADYEKHKVYACE SKAKGQPREPQVYTLPP SREEMTKNQVSLTCLVKGFYP SDIAV
VTHQGLSSPVTKSFNRGEC EWE SNGQPENNYKTTPPVLD SD
GSFFLY SKLTVD KSRWQQ GN
VFSCSVMHEALHNHYTQKSLSLSPGK
(SEQ ID NO: 98) (SEQ ID NO: 99) [hu anti- GAAATAGTGATGACGCAGTCT
CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
<huGIPR> CCAGCCACCCTGTCTGTGTCT
TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGGATTCA
2G10.344 CCAGGGGAAAGAGCCACCCT
CCTTCAGTAACTATGGCATGCACTGGGTCCGCCAGGCTCCA
VK3 (1-236) CTCCTGCAGGGCCAGTCAGAG

VL]::huKLC NA TGTTAGTAGCCACTTAGCCTG AAGTGATAAATACTATGCAGACGCCGTGAAGGGCCGATTCA
-CL + [hu GTACCAGCAGAAACCTGGCC
CCATCTCCAGAGACAACTCCAAGAACACGCTGTATCTGCAA
g anti- AGGCTCCCAGGCTCCTCATCT
ATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTG
<huGIPR> ACGAAGCAGCCACCAGGGCC
TGCGAGAGATATTGCGATTTTTGGAGTGGTCCCCGACTACT
2G10.325 ACTGGTATCCCAGCCAGGTTC
GGGGCCAGGGAACCCTGGTCACCGTGTCTAGTGCCTCCACC oe oe VH3 (1-472) AGTGGCAGTGGGTCTGGGAC
AAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAG
VH]::huIgG1 AGAGTTCACTCTCACCATCAG
CACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGG
zSEFL2-2 CAGCCTGCAGTCTGAAGATTT
ACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
(mAb); LMR TGCAGTTTATTACTGTCAGCA
GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
ID: SS- GTATCAGCAGTGGCCTCTCAC
GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC

CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTG
GGAGATCAAACGAACGGTGG AATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTG
CTGCACCATCTGTCTTCATCTT AGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGC
CCCGCCATCTGATGAGCAGTT CCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTC
GAAATCTGGAACTGCCTCTGT CCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCC
TGTGTGCCTGCTGAATAACTT TGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACC
CTATCCCAGAGAGGCCAAAG CTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTG
TACAGTGGAAGGTGGATAAC CATAATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCA
GCCCTCCAATCGGGTAACTCC GCACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAG
CAGGAGAGTGTCACAGAGCA GACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCA
GGACAGCAAGGACAGCACCT ACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAA
ACAGCCTCAGCAGCACCCTGA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCC
CGCTGAGCAAAGCAGACTAC CCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTG
GAGAAACACAAAGTCTACGC ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGT
CTGCGAAGTCACCCATCAGGG GGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAG
CCTGAGCTCGCCCGTCACAAA ACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTC
GAGCTTCAACAGGGGAGAGT TATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGG
GT
GGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCAC
AACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAA
A
(SEQ ID NO: 100) (SEQ ID NO: 101) EIVMTQSPATLSVSPGERATLS QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMHWVRQAP
CRASQSVSSHLAWYQQKPGQA GEGLEWVAAIWFDASDKYYADAVKGRFTISRDNSKNTLYLQ
PRLLIYEAATRATGIPARFSGSG MNSLRAEDTAVYYCARDIAIFGVVPDYWGQGTLVTVSSASTK
SGTEFTLTISSLQSEDFAVYYCQ GP SVFPLAP SSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALT
AA
QYQQWPLTFGGGTKVEIKRTV SGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN

AAP SVFIFPP SDEQLKSGTASVV TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
CLLNNFYPREAKVQWKVDNAL MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCE
QSGNSQESVTEQDSKDSTYSLS EQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
oe STLTLSKADYEKHKVYACEVT SKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAV
HQGLSSPVTKSFNRGEC
EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN oe oe VFSCSVMHEALHNHYTQKSLSLSPGK
(SEQ ID NO: 102) (SEQ ID NO: 103) GAAATAGTGATGACGCAGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
CCAGCCACCCTGTCTGTGTCT TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGGATTCA
CCAGGGGAAAGAGCCACCCT CCTTCAGTAACTATGGCATGCACTGGGTCCGCCAGGCTCCA
oe CTCCTGCAGGGCCAGTCAGAG GGCGAGGGGCTGGAGTGGGTGGCAGCTATATGGTTTGATGC
TGTTTTCACGCACTTAGCCTG AAGTGATAAATACTATGCAGACGCCGTGAAGGGCCGATTCA
GTACCAGCAGAAACCTGGCC CCATCTCCAGAGACAACTCCAAGAACACGCTGTATCTGCAA
AGGCTCCCAGGCTCCTCATCT ATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTG
ACGAAGCAGCCACCAGGGCC TGCGAGAGATTTGGCGATTTTTGGAGTGGTCCCCGACTACT
ACTGGTATCCCAGCCAGGTTC GGGGCCAGGGAACCCTGGTCACCGTGTCTAGTGCCTCCACC
[hu anti- AGTGGCAGTGGGTCTGGGAC
AAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAG
<huGIPR> AGAGTTCACTCTCACCATCAG
CACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGG
2G10.310 CAGCCTGCAGTCTGAAGATTT
ACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
VK3 (1-236) TGCAGTTTATTACTGTCAGCA
GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
VL]::huKLC GTATAACAACTGGCCTCTCAC
GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC
-CL + TTTCGGCGGAGGGACCAAGGT
CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTG
[Unknown GGAGATCAAACGAACGGTGG
AATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTG
anti- CTGCACCATCTGTCTTCATCTT
AGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGC
<huGIPR> NACCCGCCATCTGATGAGCAGTT CCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTC
2G10.610 GAAATCTGGAACTGCCTCTGT
CCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCC
VH3 (1-472) TGTGTGCCTGCTGAATAACTT
TGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACC
VH]::huIgG1 CTATCCCAGAGAGGCCAAAG
CTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTG
zSEFL2-2 TACAGTGGAAGGTGGATAAC
CATAATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCA
(mAb); LMR GCCCTCCAATCGGGTAACTCC
GCACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAG
ID: SS- CAGGAGAGTGTCACAGAGCA
GACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCA

ACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAA
ACAGCCTCAGCAGCACCCTGA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCC
CGCTGAGCAAAGCAGACTAC CCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTG
GAGAAACACAAAGTCTACGC ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGT
CTGCGAAGTCACCCATCAGGG GGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAG

CCTGAGCTCGCCCGTCACAAA ACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTC
GAGCTTCAACAGGGGAGAGT TATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGG
GT
GGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCAC
oe AACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAA
A
oe cr oe (SEQ ID NO: 104) (SEQ ID NO: 105) EIVMTQ SP ATL SVSPGERATLS QVQLVE SGGGVVQPGRSLRL SCAASGFTFSNYGMHWVRQAP
CRASQSVFTHLAWYQQKPGQA GEGLEWVAAIWFDASDKYYADAVKGRFTISRDNSKNTLYLQ
PRLLIYEAATRATGIPARFSGSG MNSLRAEDTAVYYCARDLAIFGVVPDYWGQGTLVTVSSASTK
SGTEFTLTIS SLQSEDFAVYYCQ GP SVFPL AP S SKST S GGTAALGCL VKDYFPEPVTVSWN S GAL T
oe QYNNWPLTFGGGTKVEIKRTV SGVHTFPAVLQS SGLY SLS SVVTVP S S SLGTQTYICNVNHKP SN
AAP SVFIFPP SDEQLKSGTASVV TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
AA
CLLNNFYPREAKVQWKVDNAL MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCE
QSGNSQESVTEQD SKD STY SL S EQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
STLTLSKADYEKHKVYACEVT SKAKGQPREPQVYTLPP SREEMTKNQVSLTCLVKGFYP SDIAV
HQGL S SPVTKSFNRGEC EWE SNGQPENNYKTTPPVLD SD
GSFFLY SKL TVD KSRWQQ GN
VFSCSVMHEALHNHYTQKSLSLSPGK
(SEQ ID NO: 106) (SEQ ID NO: 107) GAAATAGTGATGACGCAGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
CCAGCCACCCTGTCTGTGTCT TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGGATTCA
CCAGGGGAAAGAGCCACCCT CCTTCAGTAACTATGGCATGCACTGGGTCCGCCAGGCTCCA
p [Unknown CTCCTGCAGGGCCAGTCAGAG
GGCGAGGGGCTGGAGTGGGTGGCAGCTATATGGTTTGATGC
anti- TGTTTTCACGCACTTAGCCTG
AAGTGATAAATACTATGCAGACGCCGTGAAGGGCCGATTCA
<huGIPR> GTACCAGCAGAAACCTGGCC
CCATCTCCAGAGACAACTCCAAGAACACGCTGTATCTGCAA
2G10.610 AGGCTCCCAGGCTCCTCATCT
ATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTG
VK3 (1-236) ACGAAGCAGCCACCAGGGCC
TGCGAGAGATTTGGCGATTTTTGGAGTGGTCCCCGACTACT
VL]::huKLC ACTGGTATCCCAGCCAGGGTC
GGGGCCAGGGAACCCTGGTCACCGTGTCTAGTGCCTCCACC
-CL + AGTGGCAGTGGGTCTGGGAC
AAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAG
[Unknown AGAGTTCACTCTCACCATCAG
CACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGG
anti- NA CAGCCTGCAGTCTGAAGATTT
ACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
<huGIPR> TGCAGTTTATTACTGTCAGCA
GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
2G10.610 GTATAACAACTGGCCTCTCAC
GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC
VH3 (1-472) TTTCGGCGGAGGGACCAAGGT
CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTG
VH]::huIgG1 GGAGATCAAACGAACGGTGG
AATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTG
zSEFL2-2 CTGCACCATCTGTCTTCATCTT
AGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGC
(mAb); LMR CCCGCCATCTGATGAGCAGTT
CCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTC

ID: SS- GAAATCTGGAACTGCCTCTGT
CCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCC

TGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACC
`z.
CTATCCCAGAGAGGCCAAAG CTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTG
oe TACAGTGGAAGGTGGATAAC CATAATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCA
GCCCTCCAATCGGGTAACTCC GCACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAG
oe oe CAGGAGAGTGTCACAGAGCA GACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCA
GGACAGCAAGGACAGCACCT ACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAA
ACAGCCTCAGCAGCACCCTGA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCC
CGCTGAGCAAAGCAGACTAC CCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTG
GAGAAACACAAAGTCTACGC ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGT
CTGCGAAGTCACCCATCAGGG GGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAG
CCTGAGCTCGCCCGTCACAAA ACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTC
GAGCTTCAACAGGGGAGAGT TATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGG
GT
GGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCAC
AACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAA
A
(SEQ ID NO: 108) (SEQ ID NO: 109) EIVMTQ SP ATL SVSPGERATLS QVQLVE SGGGVVQPGRSLRL SCAA S GFTF SNYGMHWVRQ AP
CRASQSVFTHLAWYQQKPGQA GEGLEWVAAIWFDASDKYYADAVKGRFTISRDNSKNTLYLQ
PRLLIYEAATRATGIPARVSGSG MNSLRAEDTAVYYCARDLAIFGVVPDYWGQGTLVTVSSASTK
SGTEFTLTIS SLQSEDFAVYYCQ GP SVFPL AP S SKST S GGT AALGCL VKDYFPEPVTVSWN S GAL
T
QYNNWPLTFGGGTKVEIKRTV SGVHTFPAVLQS SGLY SLS SVVTVP S S SLGTQTYICNVNHKP SN
AA AAP SVFIFPP SDEQLKSGTASVV
TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
CLLNNFYPREAKVQWKVDNAL MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCE
QSGNSQESVTEQD SKD STY SL S EQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
STLTLSKADYEKHKVYACEVT SKAKGQPREPQVYTLPP SREEMTKNQVSLTCLVKGFYP SDIAV
HQGL S SPVTKSFNRGEC EWE SNGQPENNYKTTPPVLD SD
GSFFLY SKL TVD KSRWQQ GN
VFSCSVMHEALHNHYTQKSLSLSPGK
(SEQ ID NO: 110) (SEQ ID NO: 111) [hu anti- GAAATAGTGATGACGCAGTCT
CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
<huGIPR> CCAGCCACCCTGTCTGTGTCT
TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGGATTCA
2G10.302 CCAGGGGAAAGAGCCACCCT
CCTTCAGTAACTATGGCATGCACTGGGTCCGCCAGGCTCCA
VK3 (1-236) CTCCTGCAGGGCCAGTCAGAG
GGCGAGGGGCTGGAGTGGGTGGCAGCTATATGGTTTGATGC
VL]::huKLC TGTTTTTGAACACTTAGCCTG
AAGTGATAAATACTATGCAGACGCCGTGAAGGGCCGATTCA
-CL + NA GTACCAGCAGAAACCTGGCC
CCATCTCCAGAGACAACTCCAAGAACACGCTGTATCTGCAA
[Unknown AGGCTCCCAGGCTCCTCATCT

anti- ACGAAGCAGCCACCAGGGCC
TGCGAGAGATTTGGCGATTTTTGGAGTGGTCCCCGACTACT
<huGIPR> ACTGGTATCCCAGCCAGGTTC
GGGGCCAGGGAACCCTGGTCACCGTGTCTAGTGCCTCCACC
re) 2G10.610 AGTGGCAGTGGGTCTGGGAC
AAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAG
VH3 (1-472) AGAGTTCACTCTCACCATCAG
CACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGG
VH]::huIgG1 CAGCCTGCAGTCTGAAGATTT
ACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC oe oe zSEFL2-2 TGCAGTTTATTACTGTCAGCA
GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
(mAb); LMR GTATAACAACTGGCCTCTCAC
GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC
ID: SS- TTTCGGCGGAGGGACCAAGGT
CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTG

AATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTG
CTGCACCATCTGTCTTCATCTT AGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGC
CCCGCCATCTGATGAGCAGTT CCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTC
GAAATCTGGAACTGCCTCTGT CCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCC
TGTGTGCCTGCTGAATAACTT TGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACC
CTATCCCAGAGAGGCCAAAG CTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTG
TACAGTGGAAGGTGGATAAC CATAATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCA
GCCCTCCAATCGGGTAACTCC GCACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAG
CAGGAGAGTGTCACAGAGCA GACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCA
GGACAGCAAGGACAGCACCT ACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAA
ACAGCCTCAGCAGCACCCTGA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCC
CGCTGAGCAAAGCAGACTAC CCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTG
GAGAAACACAAAGTCTACGC ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGT
CTGCGAAGTCACCCATCAGGG GGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAG
CCTGAGCTCGCCCGTCACAAA ACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTC
GAGCTTCAACAGGGGAGAGT TATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGG
GT
GGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCAC
AACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAA
A
(SEQ ID NO: 112) (SEQ ID NO: 113) EIVMTQSPATLSVSPGERATLS QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMHWVRQAP
CRASQSVFEHLAWYQQKPGQA GEGLEWVAAIWFDASDKYYADAVKGRFTISRDNSKNTLYLQ
PRLLIYEAATRATGIPARFSGSG MNSLRAEDTAVYYCARDLAIFGVVPDYWGQGTLVTVSSASTK
SGTEFTLTISSLQSEDFAVYYCQ GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALT
QYNNWPLTFGGGTKVEIKRTV SGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN
AA AAPSVFIFPPSDEQLKSGTASVV TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
CLLNNFYPREAKVQWKVDNAL MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCE
QSGNSQESVTEQDSKDSTYSLS EQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI

STLTLSKADYEKHKVYACEVT SKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAV
HQGLSSPVTKSFNRGEC
EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN
VFSCSVMHEALHNHYTQKSLSLSPGK
oe (SEQ ID NO: 114) (SEQ ID NO: 115) " [hu anti- NA GAAATAGTGATGACGCAGTCT
CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC oe oe <huGIPR> CCAGCCACCCTGTCTGTGTCT
TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGGATTCA
2G10.329 CCAGGGGAAAGAGCCACCCT
CCTTCAGTAACTATGGCATGCACTGGGTCCGCCAGGCTCCA
VK3 (1-236) CTCCTGCAGGGCCAGTCAGAG
GGCGAGGGGCTGGAGTGGGTGGCAGCTATATGGTTTGATGC
VL]::huKLC TGTTGAACAGCACTTAGCCTG
AAGTGATAAATACTATGCAGACGCCGTGAAGGGCCGATTCA
-CL + GTACCAGCAGAAACCTGGCC
CCATCTCCAGAGACAACTCCAAGAACACGCTGTATCTGCAA
[Unknown AGGCTCCCAGGCTCCTCATCT
ATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTG
anti- ACGAAGCAGCCACCAGGGCC
TGCGAGAGATTTGGCGATTTTTGGAGTGGTCCCCGACTACT
<huGIPR> ACTGGTATCCCAGCCAGGTTC
GGGGCCAGGGAACCCTGGTCACCGTGTCTAGTGCCTCCACC
2G10.610 AGTGGCAGTGGGTCTGGGAC
AAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAG
VH3 (1-472) AGAGTTCACTCTCACCATCAG
CACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGG
VH]::huIgG1 CAGCCTGCAGTCTGAAGATTT
ACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
zSEFL2-2 TGCAGTTTATTACTGTCAGCA
GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
(mAb); LMR GTATAACAACTGGCCTCTCAC
GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC
ID: SS- TTTCGGCGGAGGGACCAAGGT
CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTG

AATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTG
CTGCACCATCTGTCTTCATCTT AGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGC
CCCGCCATCTGATGAGCAGTT CCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTC
GAAATCTGGAACTGCCTCTGT CCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCC
TGTGTGCCTGCTGAATAACTT TGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACC
CTATCCCAGAGAGGCCAAAG CTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTG
TACAGTGGAAGGTGGATAAC CATAATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCA
GCCCTCCAATCGGGTAACTCC GCACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAG
CAGGAGAGTGTCACAGAGCA GACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCA
GGACAGCAAGGACAGCACCT ACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAA
ACAGCCTCAGCAGCACCCTGA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCC
CGCTGAGCAAAGCAGACTAC CCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTG
GAGAAACACAAAGTCTACGC ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGT
CTGCGAAGTCACCCATCAGGG GGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAG
CCTGAGCTCGCCCGTCACAAA ACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTC
GAGCTTCAACAGGGGAGAGT TATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGG
GT
GGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCAC

AACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAA
A
(SEQ ID NO: 116) (SEQ ID NO: 117) oe AA EIVMTQ SP ATL SVSPGERATLS QVQLVE SGGGVVQPGRSLRL SCAA S
GFTF SNYGMHWVRQ AP
CRASQSVEQHLAWYQQKPGQ GEGLEWVAAIWFDASDKYYADAVKGRFTISRDNSKNTLYLQ
oe oe APRLLIYEAATRATGIPARFSGS MNSLRAEDTAVYYCARDLAIFGVVPDYWGQGTLVTVSSASTK
GSGTEFTLTISSLQSEDFAVYYC GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALT
QQYNNWPLTFGGGTKVEIKRT SGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN
VAAPSVFIFPPSDEQLKSGTASV TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
VCLLNNFYPREAKVQWKVDN MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCE
ALQSGNSQESVTEQDSKDSTYS EQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
LSSTLTLSKADYEKHKVYACE SKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAV
VTHQGLSSPVTKSFNRGEC
EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN
VFSCSVMHEALHNHYTQKSLSLSPGK
(SEQ ID NO: 118) (SEQ ID NO: 119) GAAATAGTGATGACGCAGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
CCGGCCACCCTGTCTGTGTCT TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGGATTCA
CCAGGGGAAAGAGCCACCCT CCTTCAGTAACTATGGCATGCACTGGGTCCGCCAGGCTCCA
CTCCTGCAGGGCCAGTCAGAG GGCGAGGGGCTGGAGTGGGTGGCAGCTATATGGTTTGATGC
TGTTCATAGCCACTTAGCCTG AAGTGATAAATACTATGCAGACGCCGTGAAGGGCCGATTCA
[hu anti- GTACCAGCAGAAACCTGGCC
CCATCTCCAGAGACAACTCCAAGAACACGCTGTATCTGCAA
<huGIPR> AGGCTCCCAGGCTCCTCATCT
ATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTG
2G10.327 ACGAAGCAGCCACCAGGGCC
TGCGAGAGATTTGGCGATTTTTGGAGTGGTCCCCGACTACT
VK3 (1-236) ACTGGTATCCCAGCCAGGTTC
GGGGCCAGGGAACCCTGGTCACCGTGTCTAGTGCCTCCACC
VL]::huKLC AGTGGCAGTGGGTCTGGGAC
AAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAG
-CL + AGAGTTCACTCTCACCATCAG
CACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGG
[Unknown CAGCCTGCAGTCTGAAGATTT
ACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
anti- A N TGCAGTTTATTACTGTCAGCA
GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
<huGIPR> GTATAACCAGTGGCCTCTCAC
GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC
2G10.610 TTTCGGCGGAGGGACCAAGGT
CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTG
VH3 (1-472) GGAGATCAAACGAACGGTGG
AATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTG
VH]::huIgG1 CTGCACCATCTGTCTTCATCTT
AGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGC
zSEFL2-2 CCCGCCATCTGATGAGCAGTT
CCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTC
(mAb); LMR GAAATCTGGAACTGCCTCTGT
CCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCC
ID: SS- TGTGTGCCTGCTGAATAACTT
TGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACC

CTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTG

TACAGTGGAAGGTGGATAAC CATAATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCA
GCCCTCCAATCGGGTAACTCC GCACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAG
CAGGAGAGTGTCACAGAGCA GACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCA
oe GGACAGCAAGGACAGCACCT ACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAA
ACAGCCTCAGCAGCACCCTGA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCC
oe oe CGCTGAGCAAAGCAGACTAC CCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTG
GAGAAACACAAAGTCTACGC ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGT
CTGCGAAGTCACCCATCAGGG GGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAG
CCTGAGCTCGCCCGTCACAAA ACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTC
GAGCTTCAACAGGGGAGAGT TATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGG
GT
GGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCAC
AACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAA
A
(SEQ ID NO: 120) (SEQ ID NO: 121) EIVMTQ SP ATL SVSPGERATLS QVQLVE SGGGVVQPGRSLRL SCAASGFTFSNYGMHWVRQAP
CRASQSVHSHLAWYQQKPGQ GEGLEWVAAIWFDASDKYYADAVKGRFTISRDNSKNTLYLQ
APRLLIYEAATRATGIPARFSGS MNSLRAEDTAVYYCARDLAIFGVVPDYWGQGTLVTVSSASTK
GS GTEFTL TI S SLQSEDFAVYYC GP SVFPL AP S SKST S GGT AALGCL VKDYFPEPVTVSWN S
GAL T
QQYNQWPLTFGGGTKVEIKRT SGVHTFPAVLQS SGLY SLS SVVTVP S S SLGTQTYICNVNHKP SN
AA VAAPSVFIFPPSDEQLKSGTASV TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
VCLLNNFYPREAKVQWKVDN MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCE
ALQSGNSQESVTEQDSKDSTYS EQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
L SSTLTL SKADYEKHKVYACE SKAKGQPREPQVYTLPP SREEMTKNQVSLTCLVKGFYP SDIAV
VTHQGLSSPVTKSFNRGEC
EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN
VFSCSVMHEALHNHYTQKSLSLSPGK
(SEQ ID NO: 122) (SEQ ID NO: 123) [hu anti- GAAATAGTGATGACGCAGTCT
CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
<huGIPR> CCAGCCACCCTGTCTGTGTCT
TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGGATTCA
2G10.338 CCAGGGGAAAGAGCCACCCT
CCTTCAGTAACTATGGCATGCACTGGGTCCGCCAGGCTCCA
VK3 (1-236) CTCCTGCAGGGCCAGTCAGAG
GGCGAGGGGCTGGAGTGGGTGGCAGCTATATGGTTTGATGC
VL]::huKLC TGTTCATCATCACTTAGCCTG
AAGTGATAAATACTATGCAGACGCCGTGAAGGGCCGATTCA
-CL + GTACCAGCAGAAACCTGGCC
CCATCTCCAGAGACAACTCCAAGAACACGCTGTATCTGCAA
[Unknown AGGCTCCCAGGCTCCTCATCT
ATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTG
anti- NA ACGAAGCAGCCACCAGGGCC
TGCGAGAGATTTGGCGATTTTTGGAGTGGTCCCCGACTACT
<huGIPR> ACTGGTATCCCAGCCAGGTTC
GGGGCCAGGGAACCCTGGTCACCGTGTCTAGTGCCTCCACC
2G10.610 AGTGGCAGTGGGTCTGGGAC

VH3 (1-472) AGAGTTCACTCTCACCATCAG
CACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGG
VH]::huIgG1 CAGCCTGCAGTCTGAAGATTT
ACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
re) GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
(mAb); LMR GTATAACCAGTGGCCTCTCAC
GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC
ID: SS- TTTCGGCGGAGGGACCAAGGT
CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTG oe oe AATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTG
CTGCACCATCTGTCTTCATCTT AGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGC
CCCGCCATCTGATGAGCAGTT CCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTC

GAAATCTGGAACTGCCTCTGT CCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCC
n.) o TGTGTGCCTGCTGAATAACTT TGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACC
oe i-J
CTATCCCAGAGAGGCCAAAG CTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTG
c,.) --.1 TACAGTGGAAGGTGGATAAC CATAATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCA
o vo GCCCTCCAATCGGGTAACTCC GCACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAG
--.1 CAGGAGAGTGTCACAGAGCA GACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCA
GGACAGCAAGGACAGCACCT ACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAA
ACAGCCTCAGCAGCACCCTGA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCC
CGCTGAGCAAAGCAGACTAC CCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTG
GAGAAACACAAAGTCTACGC ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGT
CTGCGAAGTCACCCATCAGGG GGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAG
CCTGAGCTCGCCCGTCACAAA ACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTC
GAGCTTCAACAGGGGAGAGT TATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGG
P
GT
GGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCAC o AACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAA
.
, A'.
(SEQ ID NO: 124) (SEQ ID NO: 125) " EIVMTQSPATLSVSPGERATLS
QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMHWVRQAP y , CRASQSVHHHLAWYQQKPGQ GEGLEWVAAIWFDASDKYYADAVKGRFTISRDNSKNTLYLQ
.
, APRLLIYEAATRATGIPARFSGS MNSLRAEDTAVYYCARDLAIFGVVPDYWGQGTLVTVSSASTK
, GSGTEFTLTISSLQSEDFAVYYC GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALT
QQYNQWPLTFGGGTKVEIKRT SGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN
VAAPSVFIFPPSDEQLKSGTASV TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
AA
VCLLNNFYPREAKVQWKVDN MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCE
ALQSGNSQESVTEQDSKDSTYS EQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
LSSTLTLSKADYEKHKVYACE SKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAV
VTHQGLSSPVTKSFNRGEC

VFSCSVMHEALHNHYTQKSLSLSPGK
n (SEQ ID NO: 126) (SEQ ID NO: 127) cp ,- [hu anti- GAAATAGTGATGACGCAGTCT
CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC n.) o re) c> <huGIPR> NA CCAGCCACCCTGTCTGTGTCT TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGGATTCA
oe 2G10.314 CCAGGGGAAAGAGCCACCCT
CCTTCAGTAACTATGGCATGCACTGGGTCCGCCAGGCTCCA 'a ' VK3 (1-236) CTCCTGCAGGGCCAGTCAGAG
GGCGAGGGGCTGGAGTGGGTGGCAGCTATATGGTTTGATGC oe c:
oe VL]::huKLC TGTTCATAGCCACTTAGCCTG
AAGTGATAAATACTATGCAGACGCCGTGAAGGGCCGATTCA
-CL + GTACCAGCAGAAACCTGGCC
CCATCTCCAGAGACAACTCCAAGAACACGCTGTATCTGCAA
[Unknown AGGCTCCCAGGCTCCTCATCT
ATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTG
anti- ACGAAGCAGCCACCAGGGCC
TGCGAGAGATTTGGCGATTTTTGGAGTGGTCCCCGACTACT
<huGIPR> ACTGGTATCCCAGCCAGGTTC
GGGGCCAGGGAACCCTGGTCACCGTGTCTAGTGCCTCCACC
2G10.610 AGTGGCAGTGGGTCTGGGAC
AAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAG
VH3 (1-472) AGAGTTCACTCTCACCATCAG
CACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGG
VH]::huIgG1 CAGCCTGCAGTCTGAAGATTT
ACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
zSEFL2-2 TGCAGTTTATTACTGTCAGCA
GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
(mAb); LMR GTATAACAACTGGCCTCTCAC
GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC
ID: SS- TTTCGGCGGAGGGACCAAGGT
CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTG

AATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTG
CTGCACCATCTGTCTTCATCTT AGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGC
CCCGCCATCTGATGAGCAGTT CCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTC
GAAATCTGGAACTGCCTCTGT CCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCC
TGTGTGCCTGCTGAATAACTT TGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACC
CTATCCCAGAGAGGCCAAAG CTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTG
TACAGTGGAAGGTGGATAAC CATAATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCA
GCCCTCCAATCGGGTAACTCC GCACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAG
CAGGAGAGTGTCACAGAGCA GACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCA
GGACAGCAAGGACAGCACCT ACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAA
ACAGCCTCAGCAGCACCCTGA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCC
CGCTGAGCAAAGCAGACTAC CCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTG
GAGAAACACAAAGTCTACGC ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGT
CTGCGAAGTCACCCATCAGGG GGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAG
CCTGAGCTCGCCCGTCACAAA ACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTC
GAGCTTCAACAGGGGAGAGT TATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGG
GT
GGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCAC
AACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAA
A
(SEQ ID NO: 128) (SEQ ID NO: 129) EIVMTQSPATLSVSPGERATLS QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMHWVRQAP
CRASQSVHSHLAWYQQKPGQ GEGLEWVAAIWFDASDKYYADAVKGRFTISRDNSKNTLYLQ
AA APRLLIYEAATRATGIPARFSGS MNSLRAEDTAVYYCARDLAIFGVVPDYWGQGTLVTVSSASTK
oe GSGTEFTLTISSLQSEDFAVYYC GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALT
QQYNNWPLTFGGGTKVEIKRT SGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN
oe oe VAAPSVFIFPPSDEQLKSGTASV TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
VCLLNNFYPREAKVQWKVDN MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCE
ALQSGNSQESVTEQDSKDSTYS EQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
LSSTLTLSKADYEKHKVYACE SKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAV
VTHQGLSSPVTKSFNRGEC
EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN
VFSCSVMHEALHNHYTQKSLSLSPGK
(SEQ ID NO: 130) (SEQ ID NO: 131) GAAATAGTGATGACGCAGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
CCAGCCACCCTGTCTGTGTCT TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGGATTCA
CCAGGGGAAAGAGCCACCCT CCTTCAGTAACTATGGCATGCACTGGGTCCGCCAGGCTCCA
CTCCTGCAGGGCCAGTCAGAG GGCGAGGGGCTGGAGTGGGTGGCAGCTATATGGTTTGATGC
TGTTGATGTCAACTTAGCCTG AAGTGATAAATACTATGCAGACGCCGTGAAGGGCCGATTCA
GTACCAGCAGAAACCTGGCC CCATCTCCAGAGACAACTCCAAGAACACGCTGTATCTGCAA
h AGGCTCCCAGGCTCCTCATCT
ATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTG
R>
[u anti-ACGAAGCAGCCACCAGGGCC TGCGAGAGATTTGGCGATTTTTGGAGTGGTCCCCGACTACT
<huGIP
2G10.337 ACTGGTATCCCAGCCAGGTTC
GGGGCCAGGGAACCCTGGTCACCGTGTCTAGTGCCTCCACC
VK3 1 236) AGTGGCAGTGGGTCTGGGAC AAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAG
- ( AGAGTTCACTCTCACCATCAG CACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGG
VL]::huKLC
CAGCCTGCAGTCTGAAGATTT ACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
-CL +
TGCAGTTTATTACTGTCAGCA GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
[Unknown GTATAACCAGTGGCCTCTCAC GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC
anti-NA TTTCGGCGGAGGGACCAAGGT CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTG
<huGIPR>
GGAGATCAAACGAACGGTGG AATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTG
2G10.610 CTGCACCATCTGTCTTCATCTT AGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGC

::huIgG1 (1-472) CCCGCCATCTGATGAGCAGTT CCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTC
VH]

CCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCC
z-2 TGTGTGCCTGCTGAATAACTT TGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACC
(mAb); LMR
CTATCCCAGAGAGGCCAAAG CTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTG
ID: SS-TACAGTGGAAGGTGGATAAC CATAATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCA

GCCCTCCAATCGGGTAACTCC GCACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAG
CAGGAGAGTGTCACAGAGCA GACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCA

GGACAGCAAGGACAGCACCT ACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAA
ACAGCCTCAGCAGCACCCTGA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCC
CGCTGAGCAAAGCAGACTAC CCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTG
oe GAGAAACACAAAGTCTACGC ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGT
CTGCGAAGTCACCCATCAGGG GGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAG
oe oe CCTGAGCTCGCCCGTCACAAA ACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTC
GAGCTTCAACAGGGGAGAGT TATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGG
GT

AACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAA
n.) o A
oe i-J
(SEQ ID NO: 132) (SEQ ID NO: 133) c,.) --.1 EIVMTQSPATLSVSPGERATLS QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMHWVRQAP
o vo CRASQSVDVNLAWYQQKPGQ GEGLEWVAAIWFDASDKYYADAVKGRFTISRDNSKNTLYLQ
--.1 APRLLIYEAATRATGIPARFSGS MNSLRAEDTAVYYCARDLAIFGVVPDYWGQGTLVTVSSASTK
GSGTEFTLTISSLQSEDFAVYYC GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALT
QQYNQWPLTFGGGTKVEIKRT SGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN
AA VAAPSVFIFPPSDEQLKSGTASV TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
VCLLNNFYPREAKVQWKVDN MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCE
ALQSGNSQESVTEQDSKDSTYS EQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
LSSTLTLSKADYEKHKVYACE SKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAV
VTHQGLSSPVTKSFNRGEC
EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN P
VFSCSVMHEALHNHYTQKSLSLSPGK
.
(SEQ ID NO: 134) (SEQ ID NO: 135) .
, GAAATAGTGATGACGCAGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
.
[hu anti- CCAGCCACCCTGTCTGTGTCT
TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGGATTCA
, <huGIPR> CCAGGGGAAAGAGCCACCCT
CCTTCAGTAACTATGGCATGCACTGGGTCCGCCAGGCTCCA
.
, , 2G10.341 CTCCTGCAGGGCCAGTCAGAG
GGCGAGGGGCTGGAGTGGGTGGCAGCTATATGGTTTGATGC .
, VK3 (1-236) TGTTGATGTCCACTTAGCCTG
AAGTGATAAATACTATGCAGACGCCGTGAAGGGCCGATTCA , VL]::huKLC GTACCAGCAGAAACCTGGCC
CCATCTCCAGAGACAACTCCAAGAACACGCTGTATCTGCAA
-CL + AGGCTCCCAGGCTCCTCATCT
ATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTG
[Unknown ACGAAGCAGCCACCAGGGCC
TGCGAGAGATTTGGCGATTTTTGGAGTGGTCCCCGACTACT
anti- NA ACTGGTATCCCAGCCAGGTTC
GGGGCCAGGGAACCCTGGTCACCGTGTCTAGTGCCTCCACC
<huGIPR> AGTGGCAGTGGGTCTGGGAC
AAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAG
2G10.610 AGAGTTCACTCTCACCATCAG
CACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGG
VH3 (1-472) CAGCCTGCAGTCTGAAGATTT

n VH]::huIgG1 TGCAGTTTATTACTGTCAGCA

zSEFL2-2 GTATAACCAGTGGCCTCTCAC
GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC
cp 4 (mAb); LMR TTTCGGCGGAGGGACCAAGGT
CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTG l=.) re) c5 ID: SS- GGAGATCAAACGAACGGTGG
AATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTG

AGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGC 'a CCCGCCATCTGATGAGCAGTT CCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTC
oe c:
oe GAAATCTGGAACTGCCTCTGT CCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCC
TGTGTGCCTGCTGAATAACTT TGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACC
CTATCCCAGAGAGGCCAAAG CTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTG
TACAGTGGAAGGTGGATAAC CATAATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCA
GCCCTCCAATCGGGTAACTCC GCACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAG
CAGGAGAGTGTCACAGAGCA GACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCA
GGACAGCAAGGACAGCACCT ACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAA
ACAGCCTCAGCAGCACCCTGA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCC
CGCTGAGCAAAGCAGACTAC CCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTG
GAGAAACACAAAGTCTACGC ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGT
CTGCGAAGTCACCCATCAGGG GGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAG
CCTGAGCTCGCCCGTCACAAA ACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTC
GAGCTTCAACAGGGGAGAGT TATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGG
GT
GGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCAC
AACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAA
A
(SEQ ID NO: 136) (SEQ ID NO: 137) EIVMTQ SP ATL SVSPGERATLS QVQLVE SGGGVVQPGRSLRL SCAASGFTFSNYGMHWVRQAP
CRASQSVDVHLAWYQQKPGQ GEGLEWVAAIWFDASDKYYADAVKGRFTISRDNSKNTLYLQ
APRLLIYEAATRATGIPARFSGS MNSLRAEDTAVYYCARDLAIFGVVPDYWGQGTLVTVSSASTK
GS GTEFTL TI S SLQSEDFAVYYC GP SVFPL AP S SKST S GGTAALGCLVKDYFPEPVTVSWN S GAL
T
QQYNQWPLTFGGGTKVEIKRT SGVHTFPAVLQS SGLY SLS SVVTVP S S SLGTQTYICNVNHKP SN
VAAPSVFIFPPSDEQLKSGTASV TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
AA
VCLLNNFYPREAKVQWKVDN MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCE
ALQSGNSQESVTEQD SKD STY S EQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
L SSTLTL SKADYEKHKVYACE SKAKGQPREPQVYTLPP SREEMTKNQVSLTCLVKGFYP SDIAV
VTHQGLSSPVTKSFNRGEC EWE SNGQPENNYKTTPPVLD SD
GSFFLY SKL TVD KSRWQQ GN
VFSCSVMHEALHNHYTQKSLSLSPGK
(SEQ ID NO: 138) (SEQ ID NO: 139) [hu anti- GAAATAGTGATGACGCAGTCT
CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
<huGIPR> CCAGCCACCCTGTCTGTGTCT

2G10.302 CCAGGGGAAAGAGCCACCCT
CCTTCAGTAACTATGGCATGCACTGGGTCCGCCAGGCTCCA
VK3 (1-236) NA CTCCTGCAGGGCCAGTCAGAG GGCGAGGGGCTGGAGTGGGTGGCAGCTATATGGTTTGATGC
re) VL]::huKLC TGTTTTTGAACACTTAGCCTG
AAGTGATAAATACTATGCAGACGCCGTGAAGGGCCGATTCA
-CL + [hu GTACCAGCAGAAACCTGGCC
CCATCTCCAGAGACAACTCCAAGAACACGCTGTATCTGCAA
" anti- AGGCTCCCAGGCTCCTCATCT
ATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTG oe oe <huGIPR> ACGAAGCAGCCACCAGGGCC
TGCGAGAGATATTGCGATTTTTGGAGTGTTTCCCGACTACTG
2G10.302 ACTGGTATCCCAGCCAGGTTC
GGGCCAGGGAACCCTGGTCACCGTGTCTAGTGCCTCCACCA
VH3 (1-472) AGTGGCAGTGGGTCTGGGAC
AGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGC
VH]::huIgG1 AGAGTTCACTCTCACCATCAG
ACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGA
zSEFL2-2 CAGCCTGCAGTCTGAAGATTT
CTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCG
(mAb); LMR TGCAGTTTATTACTGTCAGCA
CCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAG
ID: SS- GTATAACAACTGGCCTCTCAC
TCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCC

TCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAA
GGAGATCAAACGAACGGTGG TCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAG
CTGCACCATCTGTCTTCATCTT CCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCC
CCCGCCATCTGATGAGCAGTT AGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCC
GAAATCTGGAACTGCCTCTGT CCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTG
TGTGTGCCTGCTGAATAACTT AGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCT
CTATCCCAGAGAGGCCAAAG GAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCA
TACAGTGGAAGGTGGATAAC TAATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCAGC
GCCCTCCAATCGGGTAACTCC ACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAGGA
CAGGAGAGTGTCACAGAGCA CTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCAACA
GGACAGCAAGGACAGCACCT AAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCC
ACAGCCTCAGCAGCACCCTGA AAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCC
CGCTGAGCAAAGCAGACTAC ATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCT
GAGAAACACAAAGTCTACGC GCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAG
CTGCGAAGTCACCCATCAGGG TGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCA
CCTGAGCTCGCCCGTCACAAA CGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATA
GAGCTTCAACAGGGGAGAGT GCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAA
GT
CGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCA
CTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA
(SEQ ID NO: 140) (SEQ ID NO: 141) EIVMTQ SP ATL SVSPGERATLS QVQLVE SGGGVVQPGRSLRL SCAA S GFTF SNYGMHWVRQ AP
CRASQSVFEHLAWYQQKPGQA GEGLEWVAAIWFDASDKYYADAVKGRFTISRDNSKNTLYLQ
PRLLIYEAATRATGIPARFSGSG MNSLRAEDTAVYYCARDIAIFGVFPDYWGQGTLVTVSSASTK
SGTEFTLTIS SLQSEDFAVYYCQ GP SVFPL AP S SKST S GGT AALGCL VKDYFPEPVTVSWN S GAL
T

AA QYNNWPLTFGGGTKVEIKRTV SGVHTFPAVLQS SGLY SLS SVVTVP S S
SLGTQTYICNVNHKP SN
AAP SVFIFPP SDEQLKSGTASVV TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
CLLNNFYPREAKVQWKVDNAL MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCE
oe QSGNSQESVTEQD SKD STY SL S EQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
STLTLSKADYEKHKVYACEVT SKAKGQPREPQVYTLPP SREEMTKNQVSLTCLVKGFYP SDIAV
oe oe HQGLSSPVTKSFNRGEC
EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN
VFSCSVMHEALHNHYTQKSLSLSPGK
(SEQ ID NO: 142) (SEQ ID NO: 143) GAAATAGTGATGACGCAGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
CCAGCCACCCTGTCTGTGTCT TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGGATTCA
oe CCAGGGGAAAGAGCCACCCT CCTTCAGTAACTATGGCATGCACTGGGTCCGCCAGGCTCCA
CTCCTGCAGGGCCAGTCAGAG GGCGAGGGGCTGGAGTGGGTGGCAGCTATATGGTTTGATGC
TGTTTTTGAACACTTAGCCTG AAGTGATAAATACTATGCAGACGCCGTGAAGGGCCGATTCA
GTACCAGCAGAAACCTGGCC CCATCTCCAGAGACAACTCCAAGAACACGCTGTATCTGCAA
AGGCTCCCAGGCTCCTCATCT ATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTG
ACGAAGCAGCCACCAGGGCC TGCGAGAGATATTGCGATTTTTGGAGTGTTTCCCGACTACTG
ACTGGTATCCCAGCCAGGGTC GGGCCAGGGAACCCTGGTCACCGTGTCTAGTGCCTCCACCA
[hu anti- AGTGGCAGTGGGTCTGGGAC
AGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGC
<huGIPR> AGAGTTCACTCTCACCATCAG
ACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGA
2G10.602 CAGCCTGCAGTCTGAAGATTT
CTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCG
VK3 (1-236) TGCAGTTTATTACTGTCAGCA
CCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAG p VL]::huKLC GTATAACAACTGGCCTCTCAC
TCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCC
-CL + [hu TTTCGGCGGAGGGACCAAGGT
TCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAA
anti- GGAGATCAAACGAACGGTGG
TCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAG
<huGIPR> NA CTGCACCATCTGTCTTCATCTT
CCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCC
2G10.302 CCCGCCATCTGATGAGCAGTT
AGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCC
VH3 (1-472) GAAATCTGGAACTGCCTCTGT
CCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTG
VH]::huIgG1 TGTGTGCCTGCTGAATAACTT
AGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCT
zSEFL2-2 CTATCCCAGAGAGGCCAAAG
GAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCA
(mAb); LMR TACAGTGGAAGGTGGATAAC
TAATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCAGC
ID: SS- GCCCTCCAATCGGGTAACTCC
ACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAGGA

CTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCAACA
GGACAGCAAGGACAGCACCT AAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCC
ACAGCCTCAGCAGCACCCTGA AAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCC
CGCTGAGCAAAGCAGACTAC ATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCT
GAGAAACACAAAGTCTACGC GCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAG

CTGCGAAGTCACCCATCAGGG TGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCA
CCTGAGCTCGCCCGTCACAAA CGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATA
`z. GAGCTTCAACAGGGGAGAGT
GCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAA
oe GT
CGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCA
CTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA
oe cr oe (SEQ ID NO: 144) (SEQ ID NO: 145) EIVMTQSPATLSVSPGERATLS QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMHWVRQAP
CRASQSVFEHLAWYQQKPGQA GEGLEWVAAIWFDASDKYYADAVKGRFTISRDNSKNTLYLQ
PRLLIYEAATRATGIPARVSGSG MNSLRAEDTAVYYCARDIAIFGVFPDYWGQGTLVTVSSASTK
SGTEFTLTISSLQSEDFAVYYCQ GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALT
oe QYNNWPLTFGGGTKVEIKRTV SGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN
AAPSVFIFPPSDEQLKSGTASVV TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
AA
CLLNNFYPREAKVQWKVDNAL MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCE
QSGNSQESVTEQDSKDSTYSLS EQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
STLTLSKADYEKHKVYACEVT SKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAV
HQGLSSPVTKSFNRGEC
EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN
VFSCSVMHEALHNHYTQKSLSLSPGK
(SEQ ID NO: 146) (SEQ ID NO: 147) GAAATAGTGATGACGCAGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
CCAGCCACCCTGTCTGTGTCT TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGGATTCA
CCAGGGGAAAGAGCCACCCT CCTTCAGTAACTATGGCATGCACTGGGTCCGCCAGGCTCCA
p CTCCTGCAGGGCCAGTCAGAG GGCGAGGGGCTGGAGTGGGTGGCAGCTATATGGTTTGATGC
[hu anti- TGTTTTCGAACACTTAGCCTG
AAGTGATAAATACTATGCAGACGCCGTGAAGGGCCGATTCA
<huGIPR> GTACCAGCAGAAACCTGGCC
CCATCTCCAGAGACAACTCCAAGAACACGCTGTATCTGCAA
2G10.325 AGGCTCCCAGGCTCCTCATCT
ATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTG
VK3 (1-236) ACGAAGCAGCCACCAGGGCC
TGCGAGAGATATTGCGATTTTTGGAGTGGTCCCCGACTACT
VL]::huKLC ACTGGTATCCCAGCCAGGTTC
GGGGCCAGGGAACCCTGGTCACCGTGTCTAGTGCCTCCACC
-CL + [hu AGTGGCAGTGGGTCTGGGAC
AAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAG
anti- AGAGTTCACTCTCACCATCAG
CACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGG
<huGIPR> NA CAGCCTGCAGTCTGAAGATTT ACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
2G10.325 TGCAGTTTATTACTGTCAGCA
GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
VH3 (1-472) GTATAACCAGTGGCCTCTCAC
GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC
VH]::huIgG1 TTTCGGCGGAGGGACCAAGGT
CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTG
z5EFL2-2 GGAGATCAAACGAACGGTGG
AATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTG
(mAb); LMR CTGCACCATCTGTCTTCATCTT
AGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGC
ID: SS- CCCGCCATCTGATGAGCAGTT
CCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTC

CCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCC
TGTGTGCCTGCTGAATAACTT TGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACC
CTATCCCAGAGAGGCCAAAG CTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTG
oe TACAGTGGAAGGTGGATAAC CATAATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCA
GCCCTCCAATCGGGTAACTCC GCACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAG
oe oe CAGGAGAGTGTCACAGAGCA GACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCA
GGACAGCAAGGACAGCACCT ACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAA
ACAGCCTCAGCAGCACCCTGA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCC
CGCTGAGCAAAGCAGACTAC CCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTG
GAGAAACACAAAGTCTACGC ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGT
CTGCGAAGTCACCCATCAGGG GGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAG
CCTGAGCTCGCCCGTCACAAA ACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTC
GAGCTTCAACAGGGGAGAGT TATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGG
GT
GGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCAC
AACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAA
A
(SEQ ID NO: 148) (SEQ ID NO: 149) EIVMTQ SP ATL SVSPGERATLS QVQLVE SGGGVVQPGRSLRL SCAA S GFTF SNYGMHWVRQ AP
CRASQSVFEHLAWYQQKPGQA GEGLEWVAAIWFDASDKYYADAVKGRFTISRDNSKNTLYLQ
PRLLIYEAATRATGIPARFSGSG MNSLRAEDTAVYYCARDIAIFGVVPDYWGQGTLVTVSSASTK
SGTEFTLTIS SLQSEDFAVYYCQ GP SVFPL AP S SKST S GGT AALGCL VKDYFPEPVTVSWN S GAL
T
QYNQWPLTFGGGTKVEIKRTV SGVHTFPAVLQS SGLY SLS SVVTVP S S SLGTQTYICNVNHKP SN
AA AAP SVFIFPP SDEQLKSGTASVV
TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
CLLNNFYPREAKVQWKVDNAL MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCE
QSGNSQESVTEQD SKD STY SL S EQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
STLTLSKADYEKHKVYACEVT SKAKGQPREPQVYTLPP SREEMTKNQVSLTCLVKGFYP SDIAV
HQGL S SPVTKSFNRGEC EWE SNGQPENNYKTTPPVLD SD
GSFFLY SKL TVD KSRWQQ GN
VFSCSVMHEALHNHYTQKSLSLSPGK
(SEQ ID NO: 150) (SEQ ID NO: 151) [hu anti- GAAATAGTGATGACGCAGTCT
CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
<huGIPR> CCAGCCACCCTGTCTGTGTCT
TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGGATTCA
2G10.343 CCAGGGGAAAGAGCCACCCT
CCTTCAGTAACTATGGCATGCACTGGGTCCGCCAGGCTCCA
VK3 (1-236) CTCCTGCAGGGCCAGTCAGAG
GGCGAGGGGCTGGAGTGGGTGGCAGCTATATGGTTTGATGC
VL]::huKLC TGTTCTGGAACACTTAGCCTG
AAGTGATAAATACTATGCAGACGCCGTGAAGGGCCGATTCA
-CL + [hu A N GTACCAGCAGAAACCTGGCC
CCATCTCCAGAGACAACTCCAAGAACACGCTGTATCTGCAA
anti- AGGCTCCCAGGCTCCTCATCT

<huGIPR> ACGAAGCAGCCACCAGGGCC
TGCGAGAGATATTGCGATTTTTGGAGTGGTCCCCGACTACT
2G10.325 ACTGGTATCCCAGCCAGGTTC
GGGGCCAGGGAACCCTGGTCACCGTGTCTAGTGCCTCCACC
re) c5 VH3 (1-472) AGTGGCAGTGGGTCTGGGAC
AAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAG
VH]::huIgG1 AGAGTTCACTCTCACCATCAG
CACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGG
zSEFL2-2 CAGCCTGCAGTCTGAAGATTT
ACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC oe oe (mAb); LMR TGCAGTTTATTACTGTCAGCA
GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
ID: SS- GTATAACAACTGGCCTCTCAC
GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC

CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTG
GGAGATCAAACGAACGGTGG AATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTG
CTGCACCATCTGTCTTCATCTT AGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGC
CCCGCCATCTGATGAGCAGTT CCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTC
GAAATCTGGAACTGCCTCTGT CCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCC
TGTGTGCCTGCTGAATAACTT TGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACC
CTATCCCAGAGAGGCCAAAG CTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTG
TACAGTGGAAGGTGGATAAC CATAATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCA
GCCCTCCAATCGGGTAACTCC GCACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAG
CAGGAGAGTGTCACAGAGCA GACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCA
GGACAGCAAGGACAGCACCT ACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAA
ACAGCCTCAGCAGCACCCTGA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCC
CGCTGAGCAAAGCAGACTAC CCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTG
GAGAAACACAAAGTCTACGC ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGT
CTGCGAAGTCACCCATCAGGG GGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAG
CCTGAGCTCGCCCGTCACAAA ACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTC
GAGCTTCAACAGGGGAGAGT TATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGG
GT
GGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCAC
AACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAA
A
(SEQ ID NO: 152) (SEQ ID NO: 153) EIVMTQSPATLSVSPGERATLS QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMHWVRQAP
CRASQSVLEHLAWYQQKPGQA GEGLEWVAAIWFDASDKYYADAVKGRFTISRDNSKNTLYLQ
PRLLIYEAATRATGIPARFSGSG MNSLRAEDTAVYYCARDIAIFGVVPDYWGQGTLVTVSSASTK
SGTEFTLTISSLQSEDFAVYYCQ GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALT
QYNNWPLTFGGGTKVEIKRTV SGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN
AA AAPSVFIFPPSDEQLKSGTASVV TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
CLLNNFYPREAKVQWKVDNAL MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCE
QSGNSQESVTEQDSKDSTYSLS EQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI

STLTLSKADYEKHKVYACEVT SKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAV
HQGLSSPVTKSFNRGEC
EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN
VFSCSVMHEALHNHYTQKSLSLSPGK
oe (SEQ ID NO: 154) (SEQ ID NO: 155) " [hu anti- NA GAAATAGTGATGACGCAGTCT
CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC oe oe <huGIPR> CCAGCCACCCTGTCTGTGTCT
TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGGATTCA
2G10.307 CCAGGGGAAAGAGCCACCCT
CCTTCAGTAACTATGGCATGCACTGGGTCCGCCAGGCTCCA
VK3 (1-236) CTCCTGCAGGGCCAGTCAGAG
GGCGAGGGGCTGGAGTGGGTGGCAGCTATATGGTTTGATGC
VL]::huKLC TGTTGATAGACACTTAGCCTG
AAGTGATAAATACTATGCAGACGCCGTGAAGGGCCGATTCA
-CL + [hu GTACCAGCAGAAACCTGGCC
CCATCTCCAGAGACAACTCCAAGAACACGCTGTATCTGCAA
anti- AGGCTCCCAGGCTCCTCATCT
ATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTG
<huGIPR> ACGAAGCAGCCACCAGGGCC
TGCGAGAGATATTGCGATTTTTGGAGTGTTTCCCGACTACTG
2G10.302 ACTGGTATCCCAGCCAGGTTC
GGGCCAGGGAACCCTGGTCACCGTGTCTAGTGCCTCCACCA
VH3 (1-472) AGTGGCAGTGGGTCTGGGAC
AGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGC
VH]::huIgG1 AGAGTTCACTCTCACCATCAG
ACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGA
zSEFL2-2 CAGCCTGCAGTCTGAAGATTT
CTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCG
(mAb); LMR TGCAGTTTATTACTGTCAGCA
CCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAG
ID: SS- GTATAACCAGTGGCCTCTCAC
TCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCC

TCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAA
GGAGATCAAACGAACGGTGG TCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAG
CTGCACCATCTGTCTTCATCTT CCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCC
CCCGCCATCTGATGAGCAGTT AGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCC
GAAATCTGGAACTGCCTCTGT CCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTG
TGTGTGCCTGCTGAATAACTT AGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCT
CTATCCCAGAGAGGCCAAAG GAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCA
TACAGTGGAAGGTGGATAAC TAATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCAGC
GCCCTCCAATCGGGTAACTCC ACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAGGA
CAGGAGAGTGTCACAGAGCA CTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCAACA
GGACAGCAAGGACAGCACCT AAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCC
ACAGCCTCAGCAGCACCCTGA AAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCC
CGCTGAGCAAAGCAGACTAC ATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCT
GAGAAACACAAAGTCTACGC GCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAG
CTGCGAAGTCACCCATCAGGG TGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCA
CCTGAGCTCGCCCGTCACAAA CGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATA
GAGCTTCAACAGGGGAGAGT GCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAA
GT
CGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCA

CTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA
(SEQ ID NO: 156) (SEQ ID NO: 157) EIVMTQSPATLSVSPGERATLS QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMHWVRQAP
oe AA CRASQSVDRHLAWYQQKPGQ GEGLEWVAAIWFDASDKYYADAVKGRFTISRDNSKNTLYLQ
APRLLIYEAATRATGIPARFSGS MNSLRAEDTAVYYCARDIAIFGVFPDYWGQGTLVTVSSASTK
oe oe GSGTEFTLTISSLQSEDFAVYYC GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALT
QQYNQWPLTFGGGTKVEIKRT SGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN
VAAPSVFIFPPSDEQLKSGTASV TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
VCLLNNFYPREAKVQWKVDN MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCE
ALQSGNSQESVTEQDSKDSTYS EQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
LSSTLTLSKADYEKHKVYACE SKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAV
VTHQGLSSPVTKSFNRGEC
EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN
VFSCSVMHEALHNHYTQKSLSLSPGK
(SEQ ID NO: 158) (SEQ ID NO: 159) GAAATAGTGATGACGCAGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
CCAGCCACCCTGTCTGTGTCT TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGGATTCA
CCAGGGGAAAGAGCCACCCT CCTTCAGTAACTATGGCATGCACTGGGTCCGCCAGGCTCCA
CTCCTGCAGGGCCAGTCAGAG GGCGAGGGGCTGGAGTGGGTGGCAGCTATATGGTTTGATGC
TGTTAACCGGCACTTAGCCTG AAGTGATAAATACTATGCAGACGCCGTGAAGGGCCGATTCA
GTACCAGCAGAAACCTGGCC CCATCTCCAGAGACAACTCCAAGAACACGCTGTATCTGCAA
[hu anti- AGGCTCCCAGGCTCCTCATCT
ATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTG
<huGIPR> ACGAAGCAGCCACCAGGGCC
TGCGAGAGATATTGCGATTTTTGGAGTGTTTCCCGACTACTG
2G10.317 ACTGGTATCCCAGCCAGGTTC
GGGCCAGGGAACCCTGGTCACCGTGTCTAGTGCCTCCACCA
VK3 (1-236) AGTGGCAGTGGGTCTGGGAC
AGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGC
VL]::huKLC AGAGTTCACTCTCACCATCAG
ACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGA
-CL + [hu CAGCCTGCAGTCTGAAGATTT
CTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCG
anti- TGCAGTTTATTACTGTCAGCA
CCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAG
<huGIPR> NA GTATCAGCAGTGGCCTCTCAC TCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCC
2G10.302 TTTCGGCGGAGGGACCAAGGT
TCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAA
VH3 (1-472) GGAGATCAAACGAACGGTGG
TCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAG
VH]::huIgG1 CTGCACCATCTGTCTTCATCTT
CCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCC
zSEFL2-2 CCCGCCATCTGATGAGCAGTT
AGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCC
(mAb); LMR GAAATCTGGAACTGCCTCTGT
CCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTG
ID: SS- TGTGTGCCTGCTGAATAACTT
AGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCT

GAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCA
TACAGTGGAAGGTGGATAAC TAATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCAGC

GCCCTCCAATCGGGTAACTCC ACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAGGA
CAGGAGAGTGTCACAGAGCA CTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCAACA
GGACAGCAAGGACAGCACCT AAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCC
oe ACAGCCTCAGCAGCACCCTGA AAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCC
CGCTGAGCAAAGCAGACTAC ATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCT
oe oe GAGAAACACAAAGTCTACGC GCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAG
CTGCGAAGTCACCCATCAGGG TGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCA
CCTGAGCTCGCCCGTCACAAA CGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATA
GAGCTTCAACAGGGGAGAGT GCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAA
GT
CGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCA
CTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA
(SEQ ID NO: 160) (SEQ ID NO: 161) EIVMTQ SP ATL SVSPGERATLS QVQLVE SGGGVVQPGRSLRL SCAA S GFTF SNYGMHWVRQ AP
CRASQSVNRHLAWYQQKPGQ GEGLEWVAAIWFDASDKYYADAVKGRFTISRDNSKNTLYLQ
APRLLIYEAATRATGIPARFSGS MNSLRAEDTAVYYCARDIAIFGVFPDYWGQGTLVTVSSASTK
GS GTEFTL TI S SLQSEDFAVYYC GP SVFPL AP S SKST S GGT AALGCL VKDYFPEPVTVSWN S
GAL T
QQYQQWPLTFGGGTKVEIKRT SGVHTFPAVLQS SGLY SLS SVVTVP S S SLGTQTYICNVNHKP SN
AA VAAPSVFIFPPSDEQLKSGTASV TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
VCLLNNFYPREAKVQWKVDN MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCE
ALQSGNSQESVTEQDSKDSTYS EQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
L SSTLTL SKADYEKHKVYACE SKAKGQPREPQVYTLPP SREEMTKNQVSLTCLVKGFYP SDIAV
VTHQGLSSPVTKSFNRGEC
EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN
VFSCSVMHEALHNHYTQKSLSLSPGK
(SEQ ID NO: 162) (SEQ ID NO: 163) GAAATAGTGATGACGCAGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
[hu anti- CCAGCCACCCTGTCTGTGTCT
TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGGATTCA
<huGIPR> CCAGGGGAAAGAGCCACCCT
CCTTCAGTAACTATGGCATGCACTGGGTCCGCCAGGCTCCA
2G10.311 CTCCTGCAGGGCCAGTCAGAG
GGCGAGGGGCTGGAGTGGGTGGCAGCTATATGGTTTGATGC
VK3 (1-236) TGTTAACGTACACTTAGCCTG
AAGTGATAAATACTATGCAGACGCCGTGAAGGGCCGATTCA
VL]::huKLC GTACCAGCAGAAACCTGGCC
CCATCTCCAGAGACAACTCCAAGAACACGCTGTATCTGCAA
-CL + [hu AGGCTCCCAGGCTCCTCATCT
ATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTG
anti- ACCAGGCAGCCACCAGGGCC
TGCGAGAGATATTGCGATTTTTGGAGTGTTTCCCGACTACTG
<huGIPR> NA ACTGGTATCCCAGCCAGGTTC GGGCCAGGGAACCCTGGTCACCGTGTCTAGTGCCTCCACCA
2G10.302 AGTGGCAGTGGGTCTGGGAC
AGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGC
VH3 (1-472) AGAGTTCACTCTCACCATCAG
ACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGA
VH]::huIgG1 CAGCCTGCAGTCTGAAGATTT

zSEFL2-2 TGCAGTTTATTACTGTCAGCA
CCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAG
(mAb); LMR GTATAACCAGTGGCCTCTCAC
TCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCC
re) c5 ID: SS- TTTCGGCGGAGGGACCAAGGT
TCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAA

TCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAG
CTGCACCATCTGTCTTCATCTT CCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCC
oe oe CCCGCCATCTGATGAGCAGTT AGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCC
GAAATCTGGAACTGCCTCTGT CCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTG
TGTGTGCCTGCTGAATAACTT AGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCT
CTATCCCAGAGAGGCCAAAG GAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCA
TACAGTGGAAGGTGGATAAC TAATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCAGC
GCCCTCCAATCGGGTAACTCC ACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAGGA
CAGGAGAGTGTCACAGAGCA CTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCAACA
GGACAGCAAGGACAGCACCT AAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCC
ACAGCCTCAGCAGCACCCTGA AAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCC
CGCTGAGCAAAGCAGACTAC ATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCT
GAGAAACACAAAGTCTACGC GCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAG
CTGCGAAGTCACCCATCAGGG TGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCA
CCTGAGCTCGCCCGTCACAAA CGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATA
GAGCTTCAACAGGGGAGAGT GCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAA
GT
CGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCA
CTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA
(SEQ ID NO: 164) (SEQ ID NO: 165) EIVMTQ SP ATL SVSPGERATLS QVQLVE SGGGVVQPGRSLRL SCAASGFTFSNYGMHWVRQAP
CRASQSVNVHLAWYQQKPGQ GEGLEWVAAIWFDASDKYYADAVKGRFTISRDNSKNTLYLQ
APRLLIYQAATRATGIPARFSGS MNSLRAEDTAVYYCARDIAIFGVFPDYWGQGTLVTVSSASTK
GS GTEFTL TI S SLQSEDFAVYYC GP SVFPL AP S SKST S GGTAALGCLVKDYFPEPVTVSWN S GAL
T
QQYNQWPLTFGGGTKVEIKRT SGVHTFPAVLQS SGLY SLS SVVTVP S S SLGTQTYICNVNHKP SN
VAAPSVFIFPPSDEQLKSGTASV TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
AA
VCLLNNFYPREAKVQWKVDN MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCE
ALQSGNSQESVTEQD SKD STY S EQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
L SSTLTL SKADYEKHKVYACE SKAKGQPREPQVYTLPP SREEMTKNQVSLTCLVKGFYP SDIAV
VTHQGLSSPVTKSFNRGEC EWE SNGQPENNYKTTPPVLD SD
GSFFLY SKL TVD KSRWQQ GN
VFSCSVMHEALHNHYTQKSLSLSPGK
(SEQ ID NO: 166) (SEQ ID NO: 167) [hu anti- GAAATAGTGATGACGCAGTCT
CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
<huGIPR> CCAGCCACCCTGTCTGTGTCT

2G10.306 CCAGGGGAAAGAGCCACCCT
CCTTCAGTAACTATGGCATGCACTGGGTCCGCCAGGCTCCA
VK3 (1-236) NA CTCCTGCAGGGCCAGTCAGAG GGCGAGGGGCTGGAGTGGGTGGCAGCTATATGGTTTGATGC
re) VL]::huKLC TGTTCTGACGCACTTAGCCTG
AAGTGATAAATACTATGCAGACGCCGTGAAGGGCCGATTCA
-CL + [hu GTACCAGCAGAAACCTGGCC
CCATCTCCAGAGACAACTCCAAGAACACGCTGTATCTGCAA
" anti- AGGCTCCCAGGCTCCTCATCT
ATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTG oe oe <huGIPR> ACGAAGCAGCCACCAGGGCC
TGCGAGAGATATTGCGATTTTTGGAGTGATCCCCGACTACT
2G10.306 ACTGGTATCCCAGCCAGGTTC
GGGGCCAGGGAACCCTGGTCACCGTGTCTAGTGCCTCCACC
VH3 (1-472) AGTGGCAGTGGGTCTGGGAC
AAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAG
VH]::huIgG1 AGAGTTCACTCTCACCATCAG
CACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGG
zSEFL2-2 CAGCCTGCAGTCTGAAGATTT
ACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
(mAb); LMR TGCAGTTTATTACTGTCAGCA
GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
ID: SS- GTATCAGAACTGGCCTCTCAC
GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC

CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTG
GGAGATCAAACGAACGGTGG AATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTG
CTGCACCATCTGTCTTCATCTT AGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGC
CCCGCCATCTGATGAGCAGTT CCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTC
GAAATCTGGAACTGCCTCTGT CCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCC
TGTGTGCCTGCTGAATAACTT TGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACC
CTATCCCAGAGAGGCCAAAG CTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTG
TACAGTGGAAGGTGGATAAC CATAATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCA
GCCCTCCAATCGGGTAACTCC GCACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAG
CAGGAGAGTGTCACAGAGCA GACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCA
GGACAGCAAGGACAGCACCT ACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAA
ACAGCCTCAGCAGCACCCTGA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCC
CGCTGAGCAAAGCAGACTAC CCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTG
GAGAAACACAAAGTCTACGC ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGT
CTGCGAAGTCACCCATCAGGG GGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAG
CCTGAGCTCGCCCGTCACAAA ACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTC
GAGCTTCAACAGGGGAGAGT TATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGG
GT
GGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCAC
AACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAA
A
(SEQ ID NO: 168) (SEQ ID NO: 169) EIVMTQSPATLSVSPGERATLS QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMHWVRQAP
CRASQSVLTHLAWYQQKPGQA GEGLEWVAAIWFDASDKYYADAVKGRFTISRDNSKNTLYLQ
PRLLIYEAATRATGIPARFSGSG MNSLRAEDTAVYYCARDIAIFGVIPDYWGQGTLVTVSSASTKG
AA SGTEFTLTISSLQSEDFAVYYCQ PSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTS
QYQNWPLTFGGGTKVEIKRTV GVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNT
AAPSVFIFPPSDEQLKSGTASVV KVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI
oe CLLNNFYPREAKVQWKVDNAL SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQ
QSGNSQESVTEQDSKDSTYSLS YGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISK
oe oe STLTLSKADYEKHKVYACEVT AKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEW
HQGLSSPVTKSFNRGEC
ESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS
CSVMHEALHNHYTQKSLSLSPGK
(SEQ ID NO: 170) (SEQ ID NO: 171) GAAATAGTGATGACGCAGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
oe CCAGCCACCCTGTCTGTGTCT TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGGATTCA
CCAGGGGAAAGAGCCACCCT CCTTCAGTAACTATGGCATGCACTGGGTCCGCCAGGCTCCA
CTCCTGCAGGGCCAGTCAGAG GGCGAGGGGCTGGAGTGGGTGGCAGCTATATGGTTTGATGC
TGTTCTGACGCACTTAGCCTG AAGTGATAAATACTATGCAGACGCCGTGAAGGGCCGATTCA
GTACCAGCAGAAACCTGGCC CCATCTCCAGAGACAACTCCAAGAACACGCTGTATCTGCAA
AGGCTCCCAGGCTCCTCATCT ATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTG
ACGAAGCAGCCACCAGGGCC TGCGAGAGATATTGCGATTTTTGGAGTGATCCCCGACTACT
ACTGGTATCCCAGCCAGGGTC GGGGCCAGGGAACCCTGGTCACCGTGTCTAGTGCCTCCACC
[hu anti-AGTGGCAGTGGGTCTGGGAC AAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAG
<huGIPR>
AGAGTTCACTCTCACCATCAG CACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGG
2G10.606 VK3 1 236) CAGCCTGCAGTCTGAAGATTT ACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
- ( TGCAGTTTATTACTGTCAGCA GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
VL]::huKLC
GTATCAGAACTGGCCTCTCAC GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC
-CL + [hu TTTCGGCGGAGGGACCAAGGT CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTG
anti-GGAGATCAAACGAACGGTGG AATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTG
<huGIPR> NA
CTGCACCATCTGTCTTCATCTT AGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGC
2G10.306 CCCGCCATCTGATGAGCAGTT CCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTC
VH3 (1-472) GAAATCTGGAACTGCCTCTGT CCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCC
VH]::huIgG1 TGTGTGCCTGCTGAATAACTT TGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACC
zSEFL2-2 Ab); LMR CTATCCCAGAGAGGCCAAAG
CTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTG
(m SS-TACAGTGGAAGGTGGATAAC CATAATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCA

ID:
GCCCTCCAATCGGGTAACTCC GCACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAG
CAGGAGAGTGTCACAGAGCA GACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCA
GGACAGCAAGGACAGCACCT ACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAA
ACAGCCTCAGCAGCACCCTGA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCC
CGCTGAGCAAAGCAGACTAC CCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTG

GAGAAACACAAAGTCTACGC ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGT
CTGCGAAGTCACCCATCAGGG GGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAG
`z. CCTGAGCTCGCCCGTCACAAA
ACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTC
oe GAGCTTCAACAGGGGAGAGT TATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGG
GT
GGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCAC
oe cr oe AACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAA
A
(SEQ ID NO: 172) (SEQ ID NO: 173) EIVMTQ SP ATL SVSPGERATLS QVQLVE SGGGVVQPGRSLRL SCAA S GFTF SNYGMHWVRQ AP
CRASQSVLTHLAWYQQKPGQA GEGLEWVAAIWFDASDKYYADAVKGRFTISRDNSKNTLYLQ
oe PRLLIYEAATRATGIPARVSGSG MNSLRAEDTAVYYCARDIAIFGVIPDYWGQGTLVTVSSASTKG
SGTEFTLTIS SLQSEDFAVYYCQ P SVFPLAP S SKST S GGT AALGCL VKDYFPEPVTVSWN S GALT S

QYQNWPLTFGGGTKVEIKRTV GVHTFPAVLQSSGLYSLSSVVTVP SSSLGTQTYICNVNHKPSNT
AAPSVFIFPPSDEQLKSGTASVV KVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI
AA
CLLNNFYPREAKVQWKVDNAL SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQ
QSGNSQESVTEQD SKD STY SL S YGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISK
STLTLSKADYEKHKVYACEVT AKGQPREPQVYTLPP SREEMTKNQVSLTCLVKGFYP SDIAVEW
HQGL S SPVTKSFNRGEC E SNGQPENNYKTTPPVLD SD GSFFLY
SKLTVDKSRWQQGNVFS
C SVMHEALHNHYTQKSL SL SP GK
(SEQ ID NO: 174) (SEQ ID NO: 175) GAAATAGTGATGACGCAGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
p CCAGCCACCCTGTCTGTGTCT TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGGATTCA
anti- CCAGGGGAAAGAGCCACCCT
CCTTCAGTAACTATGGCATGCACTGGGTCCGCCAGGCTCCA
<huGIPR> CTCCTGCAGGGCCAGTCAGAG
GGCGAGGGGCTGGAGTGGGTGGCAGCTATATGGTTTGATGC

AAGTGATAAATACTATGCAGACGCCGTGAAGGGCCGATTCA
143 2G10_L GTACCAGCAGAAACCTGGCC
CCATCTCCAGAGACAACTCCAAGAACACGCTGTATCTGCAA
C1.005 (1- AGGCTCCCAGGCTCCTCATCT
ATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTG
237) (S 73 (85) ATGGTGCAGCCACCAGGGCC
TGCGAGAGATTTGGCGATTTTTGGAGTGGTCCCCGACTACT
A) VL + ACTGGTATCCCAGCCAGGTTC
GGGGCCAGGGAACCCTGGTCACCGTGTCTAGTGCCTCCACC
[Unknown AGTGGCAGTGGGTCTGGGAC
AAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAG
anti- NA AGAGTTCACTCTCACCATCAG
CACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGG
<huGIPR> CAGCCTGCAGTCTGAAGATTT
ACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
2G10.610 TGCAGTTTATTACTGTCAGCA
GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
VH3 (1-472) GTATAATAACTGGCCTCTCAC
GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC
VH]::huIgG1 TTTCGGCGGAGGGACCAAGGT
CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTG
z5EFL2-2 GGAGATCAAACGAACGGTGG

(mAb); LMR CTGCACCATCTGTCTTCATCTT
AGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGC
ID: SS- CCCGCCATCTGATGAGCAGTT
CCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTC
re) c:5 26224 GAAATCTGGAACTGCCTCTGT
CCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCC
oe TGTGTGCCTGCTGAATAACTT TGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACC
CTATCCCAGAGAGGCCAAAG CTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTG
oe cr oe TACAGTGGAAGGTGGATAAC CATAATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCA
GCCCTCCAATCGGGTAACTCC GCACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAG
CAGGAGAGTGTCACAGAGCA GACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCA

GGACAGCAAGGACAGCACCT ACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAA
n.) o ACAGCCTCAGCAGCACCCTGA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCC
oe i-J
CGCTGAGCAAAGCAGACTAC CCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTG
c,.) --.1 GAGAAACACAAAGTCTACGC ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGT
o vo CTGCGAAGTCACCCATCAGGG GGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAG
--.1 CCTGAGCTCGCCCGTCACAAA ACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTC
GAGCTTCAACAGGGGAGAGT TATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGG
GT
GGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCAC
AACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAA
A
(SEQ ID NO: 176) (SEQ ID NO: 177) EIVMTQ SP ATL SVSPGERATLS QVQLVE SGGGVVQPGRSLRL SCAASGFTFSNYGMHWVRQAP
CRASQ S VS SNLAWYQQKPGQA GEGLEWVAAIWFDASDKYYADAVKGRFTISRDNSKNTLYLQ
P
PRLLIYGAATRATGIPARFSGSG MNSLRAEDTAVYYCARDLAIFGVVPDYWGQGTLVTVSSASTK

SGTEFTLTIS SLQSEDFAVYYCQ GP SVFPL AP S SKST S GGT AALGCL VKDYFPEPVTVSWN S GAL
T .
, QYNNWPLTFGGGTKVEIKRTV SGVHTFPAVLQS SGLY SLS SVVTVP S S SLGTQTYICNVNHKP SN
' AA AAP SVFIFPP SDEQLKSGTASVV
TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL " CLLNNFYPREAKVQWKVDNAL
MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCE y , QSGNSQESVTEQD SKD STY SL S EQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
.
, STLTLSKADYEKHKVYACEVT SKAKGQPREPQVYTLPP SREEMTKNQVSLTCLVKGFYP SDIAV
, HQGL S SPVTKSFNRGEC EWE SNGQPENNYKTTPPVLD SD
GSFFLY SKL TVD KSRWQQ GN
VFSCSVMHEALHNHYTQKSLSLSPGK
(SEQ ID NO: 178) (SEQ ID NO: 179) anti- GAAATAGTGATGACGCAGTCT
CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
<huGIPR> CCAGCCACCCTGTCTGTGTCT
TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGGATTCA

CCTTCAGTAACTATGGCATGCACTGGGTCCGCCAGGCTCCA
143 2G1O_L CTCCTGCAGGGCCAGTCAGAG

n C1.005 (1- NA TGTTAGCAGCAACTTAGCCTG

237) (S 73 (85) GTACCAGCAGAAACCTGGCC
CCATCTCCAGAGACAACTCCAAGAACACGCTGTATCTGCAA
cp 4 A) VL + [hu AGGCTCCCAGGCTCCTCATCT
ATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTG n.) o g anti- ATGGTGCAGCCACCAGGGCC
TGCGAGAGATCAGGCGATTTTTGGAGTGGTCCCCGATTACT
<huGIPR> ACTGGTATCCCAGCCAGGTTC
GGGGCCAGGGAACCCTGGTCACCGTGTCTAGTGCCTCCACC 'a 2G10.348 AGTGGCAGTGGGTCTGGGAC
AAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAG oe c:
oe VH3 (1-472) AGAGTTCACTCTCACCATCAG
CACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGG
VH]::huIgG1 CAGCCTGCAGTCTGAAGATTT
ACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
zSEFL2-2 TGCAGTTTATTACTGTCAGCA
GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
(mAb); LMR GTATAATAACTGGCCTCTCAC
GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC
ID: SS- TTTCGGCGGAGGGACCAAGGT
CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTG

AATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTG
CTGCACCATCTGTCTTCATCTT AGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGC
CCCGCCATCTGATGAGCAGTT CCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTC
GAAATCTGGAACTGCCTCTGT CCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCC
TGTGTGCCTGCTGAATAACTT TGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACC
CTATCCCAGAGAGGCCAAAG CTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTG
TACAGTGGAAGGTGGATAAC CATAATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCA
GCCCTCCAATCGGGTAACTCC GCACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAG
CAGGAGAGTGTCACAGAGCA GACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCA
GGACAGCAAGGACAGCACCT ACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAA
ACAGCCTCAGCAGCACCCTGA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCC
CGCTGAGCAAAGCAGACTAC CCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTG
GAGAAACACAAAGTCTACGC ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGT
CTGCGAAGTCACCCATCAGGG GGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAG
CCTGAGCTCGCCCGTCACAAA ACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTC
GAGCTTCAACAGGGGAGAGT TATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGG
GT
GGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCAC
AACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAA
A
(SEQ ID NO: 180) (SEQ ID NO: 181) EIVMTQSPATLSVSPGERATLS QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMHWVRQAP
CRASQSVSSNLAWYQQKPGQA GEGLEWVAAIWFDASDKYYADAVKGRFTISRDNSKNTLYLQ
PRLLIYGAATRATGIPARFSGSG MNSLRAEDTAVYYCARDQAIFGVVPDYWGQGTLVTVSSASTK
SGTEFTLTISSLQSEDFAVYYCQ GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALT
QYNNWPLTFGGGTKVEIKRTV SGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN
AA AAPSVFIFPPSDEQLKSGTASVV TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL

CLLNNFYPREAKVQWKVDNAL MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCE
QSGNSQESVTEQDSKDSTYSLS EQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
STLTLSKADYEKHKVYACEVT SKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAV
oe HQGLSSPVTKSFNRGEC
EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN
VFSCSVMHEALHNHYTQKSLSLSPGK
oe oe (SEQ ID NO: 182) (SEQ ID NO: 183) GAAATAGTGATGACGCAGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
CCAGCCACCCTGTCTGTGTCT TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGGATTCA
CCAGGGGAAAGAGCCACCCT CCTTCAGTAACTATGGCATGCACTGGGTCCGCCAGGCTCCA
CTCCTGCAGGGCCAGTCAGAG GGCGAGGGGCTGGAGTGGGTGGCAGCTATATGGTTTGATGC
oe TGTTAGCAGCAACTTAGCCTG AAGTGATAAATACTATGCAGACGCCGTGAAGGGCCGATTCA
GTACCAGCAGAAACCTGGCC CCATCTCCAGAGACAACTCCAAGAACACGCTGTATCTGCAA
AGGCTCCCAGGCTCCTCATCT ATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTG
ATGGTGCAGCCACCAGGGCC TGCGAGAGATATTGCGATTTTTGGAGTGGTCCCCGACTACT
ACTGGTATCCCAGCCAGGTTC GGGGCCAGGGAACCCTGGTCACCGTGTCTAGTGCCTCCACC
AGTGGCAGTGGGTCTGGGAC AAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAG
anti-AGAGTTCACTCTCACCATCAG CACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGG
<huGIPR>
CAGCCTGCAGTCTGAAGATTT ACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC

TGCAGTTTATTACTGTCAGCA GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
143 2G1O_L
GTATAATAACTGGCCTCTCAC GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC
C1.005 (1-TTTCGGCGGAGGGACCAAGGT CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTG
237) (S 73 (85) GGAGATCAAACGAACGGTGG AATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTG
A) VL + [hu CTGCACCATCTGTCTTCATCTT AGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGC
anti-NA CCCGCCATCTGATGAGCAGTT CCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTC
<huGIPR>
GAAATCTGGAACTGCCTCTGT CCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCC
2G10.325 VH3(1-472) TGTGTGCCTGCTGAATAACTT TGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACC
CTATCCCAGAGAGGCCAAAG CTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTG
VH]::huIgG1 TACAGTGGAAGGTGGATAAC CATAATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCA
zSEFL2-2 GCCCTCCAATCGGGTAACTCC GCACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAG
(m b), LMR
CAGGAGAGTGTCACAGAGCA GACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCA
ID: SS-GGACAGCAAGGACAGCACCT ACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAA

ACAGCCTCAGCAGCACCCTGA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCC
CGCTGAGCAAAGCAGACTAC CCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTG
GAGAAACACAAAGTCTACGC ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGT
CTGCGAAGTCACCCATCAGGG GGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAG
CCTGAGCTCGCCCGTCACAAA ACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTC

GAGCTTCAACAGGGGAGAGT TATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGG
GT
GGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCAC
AACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAA
oe A
(SEQ ID NO: 184) (SEQ ID NO: 185) oe cr oe EIVMTQSPATLSVSPGERATLS QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMHWVRQAP
CRASQSVSSNLAWYQQKPGQA GEGLEWVAAIWFDASDKYYADAVKGRFTISRDNSKNTLYLQ
PRLLIYGAATRATGIPARFSGSG MNSLRAEDTAVYYCARDIAIFGVVPDYWGQGTLVTVSSASTK
SGTEFTLTISSLQSEDFAVYYCQ GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALT
QYNNWPLTFGGGTKVEIKRTV SGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN
AA AAPSVFIFPPSDEQLKSGTASVV TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
CLLNNFYPREAKVQWKVDNAL MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCE
QSGNSQESVTEQDSKDSTYSLS EQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
STLTLSKADYEKHKVYACEVT SKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAV
HQGLSSPVTKSFNRGEC
EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN
VFSCSVMHEALHNHYTQKSLSLSPGK
(SEQ ID NO: 186) (SEQ ID NO: 187) GAAATAGTGATGACGCAGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
CCAGCCACCCTGTCTGTGTCT TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGGATTCA
CCAGGGGAAAGAGCCACCCT CCTTCAGTAACTATGGCATGCACTGGGTCCGCCAGGCTCCA
CTCCTGCAGGGCCAGTCAGAG GGCGAGGGGCTGGAGTGGGTGGCAGCTATATGGTTTGATGC
[hu anti- TGTTAGCAGCAACTTAGCCTG
AAGTGATAAATACTATGCAGACGCCGTGAAGGGCCGATTCA
<huGIPR> GTACCAGCAGAAACCTGGCC
CCATCTCCAGAGACAACTCCAAGAACACGCTGTATCTGCAA
2G10.647 AGGCTCCCAGGCTCCTCATCT
ATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTG
VK3 (1-236) ATGGTGCAGCCACCAGGGCC
TGCGAGAGATTTGGCGATTTTTGGAGTGGTCCCCGACTACT
VL]::huKLC ACTGGTATCCCAGCCAGGGTC
GGGGCCAGGGAACCCTGGTCACCGTGTCTAGTGCCTCCACC
-CL + AGTGGCAGTGGGTCTGGGAC
AAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAG
[Unknown AGAGTTCACTCTCACCATCAG
CACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGG
anti- NA CAGCCTGCAGTCTGAAGATTT
ACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
<huGIPR> TGCAGTTTATTACTGTCAGCA
GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
2G10.610 GTATAATAACTGGCCTCTCAC
GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC
VH3 (1-472) TTTCGGCGGAGGGACCAAGGT
CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTG
VH]::huIgG1 GGAGATCAAACGAACGGTGG
AATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTG
zSEFL2-2 CTGCACCATCTGTCTTCATCTT
AGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGC
(mAb); LMR CCCGCCATCTGATGAGCAGTT
CCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTC
ID: SS- GAAATCTGGAACTGCCTCTGT
CCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCC

TGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACC
.7r CTATCCCAGAGAGGCCAAAG
CTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTG
`z. TACAGTGGAAGGTGGATAAC
CATAATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCA
oe GCCCTCCAATCGGGTAACTCC GCACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAG
CAGGAGAGTGTCACAGAGCA GACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCA
oe oe GGACAGCAAGGACAGCACCT ACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAA
ACAGCCTCAGCAGCACCCTGA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCC
CGCTGAGCAAAGCAGACTAC CCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTG
GAGAAACACAAAGTCTACGC ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGT
CTGCGAAGTCACCCATCAGGG GGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAG
CCTGAGCTCGCCCGTCACAAA ACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTC
GAGCTTCAACAGGGGAGAGT TATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGG
GT
GGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCAC
AACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAA
A
(SEQ ID NO: 188) (SEQ ID NO: 189) EIVMTQ SP ATL SVSPGERATLS QVQLVE SGGGVVQPGRSLRL SCAASGFTFSNYGMHWVRQAP
CRASQ S VS SNLAWYQQKPGQA GEGLEWVAAIWFDASDKYYADAVKGRFTISRDNSKNTLYLQ
PRLLIYGAATRATGIPARVSGS MNSLRAEDTAVYYCARDLAIFGVVPDYWGQGTLVTVSSASTK
GS GTEFTL TI S SLQSEDFAVYYC GP SVFPL AP S SKST S GGTAALGCLVKDYFPEPVTVSWN S GAL
T
QQYNNWPLTFGGGTKVEIKRT SGVHTFPAVLQS SGLY SLS SVVTVP S S SLGTQTYICNVNHKP SN
AA VAAPSVFIFPPSDEQLKSGTASV TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
VCLLNNFYPREAKVQWKVDN MI SRTPEVTCVVVDVSHEDPEVKFNWYVD GVEVHNAKTKPCE
ALQSGNSQESVTEQDSKDSTYS EQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
L SSTLTL SKADYEKHKVYACE SKAKGQPREPQVYTLPP SREEMTKNQVSLTCLVKGFYP SDIAV
VTHQGLSSPVTKSFNRGEC
EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN
VFSCSVMHEALHNHYTQKSLSLSPGK
(SEQ ID NO: 190) (SEQ ID NO: 191) [hu anti- GAAATAGTGATGACGCAGTCT
CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
<huGIPR> CCAGCCACCCTGTCTGTGTCT
TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGGATTCA
2G10.649 CCAGGGGAAAGAGCCACCCT
CCTTCAGTAACTATGGCATGCACTGGGTCCGCCAGGCTCCA
VK3 (1-236) CTCCTGCAGGGCCAGTCAGAG
GGCGAGGGGCTGGAGTGGGTGGCAGCTATATGGTTTGATGC
VL]::huKLC TGTTAGCAGCAACTTAGCCTG
AAGTGATAAATACTATGCAGACGCCGTGAAGGGCCGATTCA
-CL + [hu GTACCAGCAGAAACCTGGCC
CCATCTCCAGAGACAACTCCAAGAACACGCTGTATCTGCAA
anti- NA AGGCTCCCAGGCTCCTCATCT
ATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTG
<huGIPR> ATGAAGCAGCCACCAGGGCC

2G10.348 ACTGGTATCCCAGCCAGGGTC
GGGGCCAGGGAACCCTGGTCACCGTGTCTAGTGCCTCCACC
4 VH3 (1-472) AGTGGCAGTGGGTCTGGGAC
AAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAG
VH]::huIgG1 AGAGTTCACTCTCACCATCAG
CACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGG
zSEFL2-2 CAGCCTGCAGTCTGAAGATTT
ACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
(mAb); LMR TGCAGTTTATTACTGTCAGCA
GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA oe oe ID: SS- GTATAATAACTGGCCTCTCAC
GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC

CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTG
GGAGATCAAACGAACGGTGG AATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTG

CTGCACCATCTGTCTTCATCTT AGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGC
n.) o CCCGCCATCTGATGAGCAGTT CCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTC
oe i-J
GAAATCTGGAACTGCCTCTGT CCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCC
c,.) TGTGTGCCTGCTGAATAACTT TGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACC
o vo CTATCCCAGAGAGGCCAAAG CTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTG

TACAGTGGAAGGTGGATAAC CATAATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCA
GCCCTCCAATCGGGTAACTCC GCACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAG
CAGGAGAGTGTCACAGAGCA GACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCA
GGACAGCAAGGACAGCACCT ACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAA
ACAGCCTCAGCAGCACCCTGA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCC
CGCTGAGCAAAGCAGACTAC CCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTG
GAGAAACACAAAGTCTACGC ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGT
CTGCGAAGTCACCCATCAGGG GGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAG
P
CCTGAGCTCGCCCGTCACAAA ACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTC
o GAGCTTCAACAGGGGAGAGT TATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGG
.
GT
GGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCAC , "
AACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAA
"
, A
' , , (SEQ ID NO: 192) (SEQ ID NO: 193) .
, EIVMTQSPATLSVSPGERATLS QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMHWVRQAP
, CRASQSVSSNLAWYQQKPGQA GEGLEWVAAIWFDASDKYYADAVKGRFTISRDNSKNTLYLQ
PRLLIYEAATRATGIPARVSGSG MNSLRAEDTAVYYCARDQAIFGVVPDYWGQGTLVTVSSASTK
SGTEFTLTISSLQSEDFAVYYCQ GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALT
QYNNWPLTFGGGTKVEIKRTV SGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN
AAPSVFIFPPSDEQLKSGTASVV TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
AA
CLLNNFYPREAKVQWKVDNAL MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCE
QSGNSQESVTEQDSKDSTYSLS EQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI

STLTLSKADYEKHKVYACEVT SKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAV
n HQGLSSPVTKSFNRGEC
EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN
cp VFSCSVMHEALHNHYTQKSLSLSPGK
n.) o (SEQ ID NO: 194) (SEQ ID NO: 195) oe [hu anti-NA GAAATAGTGATGACGCAGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
'a " c= <huGIPR> CCAGCCACCCTGTCTGTGTCT
TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGGATTCA oe c:
oe 2G10.305 CCAGGGGAAAGAGCCACCCT
CCTTCAGTAACTATGGCATGCACTGGGTCCGCCAGGCTCCA
VK3 (1-236) CTCCTGCAGGGCCAGTCAGAG
GGCGAGGGGCTGGAGTGGGTGGCAGCTATATGGTTTGATGC
VL]::huKLC TGTTGATGTTAACTTAGCCTG
AAGTGATAAATACTATGCAGACGCCGTGAAGGGCCGATTCA
-CL + GTACCAGCAGAAACCTGGCC
CCATCTCCAGAGACAACTCCAAGAACACGCTGTATCTGCAA
[Unknown AGGCTCCCAGGCTCCTCATCT
ATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTG
anti- ACAACGCAGCCACCAGGGCC
TGCGAGAGATTTGGCGATTTTTGGAGTGGTCCCCGACTACT
<huGIPR> ACTGGTATCCCAGCCAGGTTC
GGGGCCAGGGAACCCTGGTCACCGTGTCTAGTGCCTCCACC
2G10.610 AGTGGCAGTGGGTCTGGGAC
AAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAG
VH3 (1-472) AGAGTTCACTCTCACCATCAG
CACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGG
VH]::huIgG1 CAGCCTGCAGTCTGAAGATTT
ACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
zSEFL2-2 TGCAGTTTATTACTGTCAGCA
GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
(mAb); LMR GTATCAGAACTGGCCTCTCAC
GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC
ID: SS- TTTCGGCGGAGGGACCAAGGT
CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTG

AATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTG
CTGCACCATCTGTCTTCATCTT AGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGC
CCCGCCATCTGATGAGCAGTT CCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTC
GAAATCTGGAACTGCCTCTGT CCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCC
TGTGTGCCTGCTGAATAACTT TGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACC
CTATCCCAGAGAGGCCAAAG CTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTG
TACAGTGGAAGGTGGATAAC CATAATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCA
GCCCTCCAATCGGGTAACTCC GCACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAG
CAGGAGAGTGTCACAGAGCA GACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCA
GGACAGCAAGGACAGCACCT ACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAA
ACAGCCTCAGCAGCACCCTGA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCC
CGCTGAGCAAAGCAGACTAC CCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTG
GAGAAACACAAAGTCTACGC ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGT
CTGCGAAGTCACCCATCAGGG GGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAG
CCTGAGCTCGCCCGTCACAAA ACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTC
GAGCTTCAACAGGGGAGAGT TATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGG
GT
GGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCAC
AACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAA

A
(SEQ ID NO: 196) (SEQ ID NO: 197) EIVMTQSPATLSVSPGERATLS QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMHWVRQAP
oe AA CRASQSVDVNLAWYQQKPGQ GEGLEWVAAIWFDASDKYYADAVKGRFTISRDNSKNTLYLQ
APRLLIYNAATRATGIPARFSGS MNSLRAEDTAVYYCARDLAIFGVVPDYWGQGTLVTVSSASTK
oe oe GSGTEFTLTISSLQSEDFAVYYC GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALT
QQYQNWPLTFGGGTKVEIKRT SGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN
VAAPSVFIFPPSDEQLKSGTASV TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
VCLLNNFYPREAKVQWKVDN MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCE
ALQSGNSQESVTEQDSKDSTYS EQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
LSSTLTLSKADYEKHKVYACE SKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAV
VTHQGLSSPVTKSFNRGEC
EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN
VFSCSVMHEALHNHYTQKSLSLSPGK
(SEQ ID NO: 198) (SEQ ID NO: 199) GAAATAGTGATGACGCAGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
CCAGCCACCCTGTCTGTGTCT TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGGATTCA
CCAGGGGAAAGAGCCACCCT CCTTCAGTAACTATGGCATGCACTGGGTCCGCCAGGCTCCA
CTCCTGCAGGGCCAGTCAGAG GGCGAGGGGCTGGAGTGGGTGGCAGCTATATGGTTTGATGC
TGTTGATGTTAACTTAGCCTG AAGTGATAAATACTATGCAGACGCCGTGAAGGGCCGATTCA
h GTACCAGCAGAAACCTGGCC
CCATCTCCAGAGACAACTCCAAGAACACGCTGTATCTGCAA
R>
[u anti-AGGCTCCCAGGCTCCTCATCT ATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTG
<huGIP
2G10.605 ACAACGCAGCCACCAGGGCC
TGCGAGAGATTTGGCGATTTTTGGAGTGGTCCCCGACTACT
ACTGGTATCCCAGCCAGGGTC GGGGCCAGGGAACCCTGGTCACCGTGTCTAGTGCCTCCACC
VK3 (1-236) AGTGGCAGTGGGTCTGGGAC AAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAG
VL]::huKLC
AGAGTTCACTCTCACCATCAG CACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGG
-CL +
CAGCCTGCAGTCTGAAGATTT ACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
[Unknown TGCAGTTTATTACTGTCAGCA GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
anti-NA GTATCAGAACTGGCCTCTCAC GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC
<huGIPR>
TTTCGGCGGAGGGACCAAGGT CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTG
2G10.610 GGAGATCAAACGAACGGTGG AATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTG
VH3 :huIgG1(1-472) CTGCACCATCTGTCTTCATCTT AGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGC
VH]:

CCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTC

z GAAATCTGGAACTGCCTCTGT CCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCC
(mAb); LMR
TGTGTGCCTGCTGAATAACTT TGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACC
ID: 26230 SS-CTATCCCAGAGAGGCCAAAG CTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTG
TACAGTGGAAGGTGGATAAC CATAATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCA

GCCCTCCAATCGGGTAACTCC GCACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAG
CAGGAGAGTGTCACAGAGCA GACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCA
`z. GGACAGCAAGGACAGCACCT
ACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAA
oe ACAGCCTCAGCAGCACCCTGA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCC
CGCTGAGCAAAGCAGACTAC CCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTG
oe oe GAGAAACACAAAGTCTACGC ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGT
CTGCGAAGTCACCCATCAGGG GGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAG
CCTGAGCTCGCCCGTCACAAA ACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTC
GAGCTTCAACAGGGGAGAGT TATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGG
GT
GGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCAC
AACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAA
A
(SEQ ID NO: 200) (SEQ ID NO: 201) EIVMTQSPATL SVSPGERATLS QVQLVE SGGGVVQPGRSLRL SCAASGFTFSNYGMHWVRQAP
CRASQSVDVNLAWYQQKPGQ GEGLEWVAAIWFDASDKYYADAVKGRFTISRDNSKNTLYLQ
APRLLIYNAATRATGIPARVSG MNSLRAEDTAVYYCARDLAIFGVVPDYWGQGTLVTVSSASTK
S GS GTEFTL TI S SLQ SEDFAVYY GP SVFPL AP S SKST S GGTAALGCLVKDYFPEPVTVSWN S
GAL T
CQQYQNWPLTFGGGTKVEIKR SGVHTFPAVLQSSGLY SLSSVVTVP SSSLGTQTYICNVNHKP SN
TVAAP SVFIFPP SDEQLKSGTAS TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
AA
VVCLLNNFYPREAKVQWKVD MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCE
NALQSGNSQESVTEQDSKDST EQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
YSL SSTLTL SKADYEKHKVYA SKAKGQPREPQVYTLPP SREEMTKNQVSLTCLVKGFYP SDIAV
CEVTHQGL SSPVTKSFNRGEC EWE SNGQPENNYKTTPPVLD SD GSFFLY SKL TVD KSRWQQ GN
VFSCSVMHEALHNHYTQKSLSLSPGK
(SEQ ID NO: 202) (SEQ ID NO: 203) h GAAATAGTGATGACGCAGTCT
CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
[u anti-CCAGCCACCCTGTCTGTGTCT TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGGATTCA
<huGIPR>
CCAGGGGAAAGAGCCACCCT CCTTCAGTAACTATGGCATGCACTGGGTCCGCCAGGCTCCA
2G10.340 VK3 1236) CTCCTGCAGGGCCAGTCAGAG GGCGAGGGGCTGGAGTGGGTGGCAGCTATATGGTTTGATGC
(-TGTTCATACGAACTTAGCCTG AAGTGATAAATACTATGCAGACGCCGTGAAGGGCCGATTCA
VL]::huKLC
GTACCAGCAGAAACCTGGCC CCATCTCCAGAGACAACTCCAAGAACACGCTGTATCTGCAA
-CL + [hu AGGCTCCCAGGCTCCTCATCT ATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTG
anti-ACAACGCAGCCACCAGGGCC TGCGAGAGATATTGCGATTTTTGGAGTGGTCCCCGACTACT
<huGIPR> NA
ACTGGTATCCCAGCCAGGTTC GGGGCCAGGGAACCCTGGTCACCGTGTCTAGTGCCTCCACC
2G10.325 VH3 1 472) AGTGGCAGTGGGTCTGGGAC AAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAG
( AGAGTTCACTCTCACCATCAG CACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGG

VH]: -:huIgG1 CAGCCTGCAGTCTGAAGATTT ACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
zSEFL=2-2 TGCAGTTTATTACTGTCAGCA GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
(mAb); LMR
GTATCAGAACTGGCCTCTCAC GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC
Itc: ID: SS-oe TTTCGGCGGAGGGACCAAGGT CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTG
==.?1 26217 GGAGATCAAACGAACGGTGG AATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTG
oe oe CTGCACCATCTGTCTTCATCTT AGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGC
CCCGCCATCTGATGAGCAGTT CCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTC
GAAATCTGGAACTGCCTCTGT CCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCC
TGTGTGCCTGCTGAATAACTT TGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACC
CTATCCCAGAGAGGCCAAAG CTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTG
TACAGTGGAAGGTGGATAAC CATAATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCA
GCCCTCCAATCGGGTAACTCC GCACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAG
CAGGAGAGTGTCACAGAGCA GACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCA
GGACAGCAAGGACAGCACCT ACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAA
ACAGCCTCAGCAGCACCCTGA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCC
CGCTGAGCAAAGCAGACTAC CCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTG
GAGAAACACAAAGTCTACGC ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGT
CTGCGAAGTCACCCATCAGGG GGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAG
CCTGAGCTCGCCCGTCACAAA ACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTC
GAGCTTCAACAGGGGAGAGT TATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGG
GT
GGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCAC
AACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAA
A
(SEQ ID NO: 204) (SEQ ID NO: 205) EIVMTQSPATLSVSPGERATLS QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMHWVRQAP
CRASQSVHTNLAWYQQKPGQ GEGLEWVAAIWFDASDKYYADAVKGRFTISRDNSKNTLYLQ
APRLLIYNAATRATGIPARFSGS MNSLRAEDTAVYYCARDIAIFGVVPDYWGQGTLVTVSSASTK
GSGTEFTLTISSLQSEDFAVYYC GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALT
QQYQNWPLTFGGGTKVEIKRT SGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN
AA VAAPSVFIFPPSDEQLKSGTASV TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
VCLLNNFYPREAKVQWKVDN MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCE
ALQSGNSQESVTEQDSKDSTYS EQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
LSSTLTLSKADYEKHKVYACE SKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAV
VTHQGLSSPVTKSFNRGEC
EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN
VFSCSVMHEALHNHYTQKSLSLSPGK
(SEQ ID NO: 206) (SEQ ID NO: 207) [hu anti- GAAATAGTGATGACGCAGTCT
CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
<huGIPR> CCAGCCACCCTGTCTGTGTCT
TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGGATTCA
re) 2G10.334 NA CCAGGGGAAAGAGCCACCCT
CCTTCAGTAACTATGGCATGCACTGGGTCCGCCAGGCTCCA
VK3 (1-236) CTCCTGCAGGGCCAGTCAGAG
GGCGAGGGGCTGGAGTGGGTGGCAGCTATATGGTTTGATGC
VL]::huKLC TGTTAACCTGAACTTAGCCTG
AAGTGATAAATACTATGCAGACGCCGTGAAGGGCCGATTCA oe oe -CL + GTACCAGCAGAAACCTGGCC
CCATCTCCAGAGACAACTCCAAGAACACGCTGTATCTGCAA
[Unknown AGGCTCCCAGGCTCCTCATCT
ATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTG
anti- ACCAGGCAGCCACCAGGGCC
TGCGAGAGATTTGGCGATTTTTGGAGTGGTCCCCGACTACT
<huGIPR> ACTGGTATCCCAGCCAGGTTC
GGGGCCAGGGAACCCTGGTCACCGTGTCTAGTGCCTCCACC
2G10.610 AGTGGCAGTGGGTCTGGGAC
AAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAG
VH3 (1-472) AGAGTTCACTCTCACCATCAG
CACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGG
VH]::huIgG1 CAGCCTGCAGTCTGAAGATTT
ACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
zSEFL2-2 TGCAGTTTATTACTGTCAGCA
GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
(mAb); LMR GTATAACCAGTGGCCTCTCAC
GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC
ID: SS- TTTCGGCGGAGGGACCAAGGT
CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTG

AATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTG
CTGCACCATCTGTCTTCATCTT AGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGC
CCCGCCATCTGATGAGCAGTT CCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTC
GAAATCTGGAACTGCCTCTGT CCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCC
TGTGTGCCTGCTGAATAACTT TGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACC
CTATCCCAGAGAGGCCAAAG CTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTG
TACAGTGGAAGGTGGATAAC CATAATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCA
GCCCTCCAATCGGGTAACTCC GCACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAG
CAGGAGAGTGTCACAGAGCA GACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCA
GGACAGCAAGGACAGCACCT ACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAA
ACAGCCTCAGCAGCACCCTGA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCC
CGCTGAGCAAAGCAGACTAC CCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTG
GAGAAACACAAAGTCTACGC ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGT
CTGCGAAGTCACCCATCAGGG GGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAG
CCTGAGCTCGCCCGTCACAAA ACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTC
GAGCTTCAACAGGGGAGAGT TATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGG
GT
GGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCAC
AACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAA
A
(SEQ ID NO: 208) (SEQ ID NO: 209) EIVMTQSPATLSVSPGERATLS QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMHWVRQAP

CRASQSVNLNLAWYQQKPGQ GEGLEWVAAIWFDASDKYYADAVKGRFTISRDNSKNTLYLQ
AA APRLLIYQAATRATGIPARFSGS MNSLRAEDTAVYYCARDLAIFGVVPDYWGQGTLVTVSSASTK
GSGTEFTLTISSLQSEDFAVYYC GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALT
oe QQYNQWPLTFGGGTKVEIKRT SGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN
VAAPSVFIFPPSDEQLKSGTASV TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
oe oe VCLLNNFYPREAKVQWKVDN MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCE
ALQSGNSQESVTEQDSKDSTYS EQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
LSSTLTLSKADYEKHKVYACE SKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAV
VTHQGLSSPVTKSFNRGEC
EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN
VFSCSVMHEALHNHYTQKSLSLSPGK
(SEQ ID NO: 210) (SEQ ID NO: 211) GAAATAGTGATGACGCAGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
CCAGCCACCCTGTCTGTGTCT TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGGATTCA
CCAGGGGAAAGAGCCACCCT CCTTCAGTAACTATGGCATGCACTGGGTCCGCCAGGCTCCA
CTCCTGCAGGGCCAGTCAGAG GGCGAGGGGCTGGAGTGGGTGGCAGCTATATGGTTTGATGC
TGTTTTCCAGAACTTAGCCTG AAGTGATAAATACTATGCAGACGCCGTGAAGGGCCGATTCA
GTACCAGCAGAAACCTGGCC CCATCTCCAGAGACAACTCCAAGAACACGCTGTATCTGCAA
AGGCTCCCAGGCTCCTCATCT ATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTG
h ACCAGGCAGCCACCAGGGCC
TGCGAGAGATATTGCGATTTTTGGAGTGGTCCCCGACTACT
R>
[u anti-ACTGGTATCCCAGCCAGGTTC GGGGCCAGGGAACCCTGGTCACCGTGTCTAGTGCCTCCACC
<huGIP
2G10.339 AGTGGCAGTGGGTCTGGGAC
AAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAG
VK3 1 -236) AGAGTTCACTCTCACCATCAG CACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGG
( CAGCCTGCAGTCTGAAGATTT ACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
VL]::huKLC
TGCAGTTTATTACTGTCAGCA GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
-CL + [hu GTATAACCAGTGGCCTCTCAC GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC
anti-TTTCGGCGGAGGGACCAAGGT CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTG
<huGIPR> NA
GGAGATCAAACGAACGGTGG AATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTG
2G10.325 CTGCACCATCTGTCTTCATCTT AGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGC
VH3 :huIgG1(1-472) CCCGCCATCTGATGAGCAGTT CCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTC
VH]:

CCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCC
z-2 Ab LMR TGTGTGCCTGCTGAATAACTT
TGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACC
(m);
SS CTATCCCAGAGAGGCCAAAG
CTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTG
-ID:
TACAGTGGAAGGTGGATAAC CATAATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCA

GCCCTCCAATCGGGTAACTCC GCACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAG
CAGGAGAGTGTCACAGAGCA GACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCA
GGACAGCAAGGACAGCACCT ACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAA

ACAGCCTCAGCAGCACCCTGA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCC
CGCTGAGCAAAGCAGACTAC CCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTG
GAGAAACACAAAGTCTACGC ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGT
oe CTGCGAAGTCACCCATCAGGG GGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAG
CCTGAGCTCGCCCGTCACAAA ACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTC
oe oe GAGCTTCAACAGGGGAGAGT TATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGG
GT
GGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCAC
AACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAA
A
(SEQ ID NO: 212) (SEQ ID NO: 213) oe EIVMTQ SP ATL SVSPGERATLS QVQLVE SGGGVVQPGRSLRL SCAASGFTFSNYGMHWVRQAP
CRASQSVFQNLAWYQQKPGQ GEGLEWVAAIWFDASDKYYADAVKGRFTISRDNSKNTLYLQ
APRLLIYQAATRATGIPARFSGS MNSLRAEDTAVYYCARDIAIFGVVPDYWGQGTLVTVSSASTK
GS GTEFTL TI S SLQSEDFAVYYC GP SVFPL AP S SKST S GGTAALGCL VKDYFPEPVTVSWN S
GAL T
QQYNQWPLTFGGGTKVEIKRT SGVHTFPAVLQS SGLY SLS SVVTVP S S SLGTQTYICNVNHKP SN
VAAPSVFIFPPSDEQLKSGTASV TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
AA
VCLLNNFYPREAKVQWKVDN MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCE
ALQSGNSQESVTEQD SKD STY S EQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
L SSTLTL SKADYEKHKVYACE SKAKGQPREPQVYTLPP SREEMTKNQVSLTCLVKGFYP SDIAV
VTHQGLSSPVTKSFNRGEC EWE SNGQPENNYKTTPPVLD SD
GSFFLY SKL TVD KSRWQQ GN
VFSCSVMHEALHNHYTQKSLSLSPGK
(SEQ ID NO: 214) (SEQ ID NO: 215) GAAATAGTGATGACGCAGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
CCAGCCACCCTGTCTGTGTCT TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGGATTCA
[hu anti- CCAGGGGAAAGAGCCACCCT
CCTTCCAGAACTATGGCATGCACTGGGTCCGCCAGGCTCCA
<huGIPR> CTCCTGCAGGGCCAGTCAGAG
GGCGAGGGGCTGGAGTGGGTGGCAGCTATATGGTTTGATGC
2G10.307 TGTTGATAGACACTTAGCCTG
GTACGGTAAATACTATGCAGACGCCGTGAAGGGCCGATTCA
VK3 (1-236) GTACCAGCAGAAACCTGGCC
CCATCTCCAGAGACAACTCCAAGAACACGCTGTATCTGCAA
VL]::huKLC AGGCTCCCAGGCTCCTCATCT
ATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTG
-CL + [hu ACGAAGCAGCCACCAGGGCC
TGCGAGAGATCAGACGATTTTTGGAGTGGTCCCCGACTACT
anti- ACTGGTATCCCAGCCAGGTTC
GGGGCCAGGGAACCCTGGTCACCGTGTCTAGTGCCTCCACC
<huGIPR> NA AGTGGCAGTGGGTCTGGGAC AAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAG
2G10.307 AGAGTTCACTCTCACCATCAG
CACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGG
VH3 (1-472) CAGCCTGCAGTCTGAAGATTT
ACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
VH]::huIgG1 TGCAGTTTATTACTGTCAGCA
GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
zSEFL2-2 GTATAACCAGTGGCCTCTCAC

(mAb); LMR TTTCGGCGGAGGGACCAAGGT
CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTG
6 ID: SS- GGAGATCAAACGAACGGTGG
AATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTG
re) c5 26184 CTGCACCATCTGTCTTCATCTT
AGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGC
oe CCCGCCATCTGATGAGCAGTT CCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTC
GAAATCTGGAACTGCCTCTGT CCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCC
oe oe TGTGTGCCTGCTGAATAACTT TGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACC
CTATCCCAGAGAGGCCAAAG CTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTG
TACAGTGGAAGGTGGATAAC CATAATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCA
GCCCTCCAATCGGGTAACTCC GCACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAG
CAGGAGAGTGTCACAGAGCA GACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCA
GGACAGCAAGGACAGCACCT ACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAA
ACAGCCTCAGCAGCACCCTGA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCC
CGCTGAGCAAAGCAGACTAC CCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTG
GAGAAACACAAAGTCTACGC ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGT
CTGCGAAGTCACCCATCAGGG GGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAG
CCTGAGCTCGCCCGTCACAAA ACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTC
GAGCTTCAACAGGGGAGAGT TATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGG
GT
GGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCAC
AACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAA
A
(SEQ ID NO: 216) (SEQ ID NO: 217) EIVMTQSPATL SVSPGERATLS QVQLVE SGGGVVQPGRSLRL SCAASGFTFQNYGMHWVRQAP
CRASQSVDRHLAWYQQKPGQ GEGLEWVAAIWFDAYGKYYADAVKGRFTISRDNSKNTLYLQ
APRLLIYEAATRATGIPARFSGS MNSLRAEDTAVYYCARDQTIFGVVPDYWGQGTLVTVSSASTK
GS GTEFTL TI S SLQ SEDFAVYYC GP SVFPL AP S SKST S GGTAALGCLVKDYFPEPVTVSWN S
GAL T
QQYNQWPLTFGGGTKVEIKRT SGVHTFPAVLQSSGLY SLSSVVTVP SSSLGTQTYICNVNHKP SN
AA VAAPSVFIFPPSDEQLKSGTASV TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
VCLLNNFYPREAKVQWKVDN MI SRTPEVTCVVVDVSHEDPEVKFNWYVD GVEVHNAKTKPCE
ALQSGNSQESVTEQD SKD STY S EQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
L SSTLTL SKADYEKHKVYACE SKAKGQPREPQVYTLPP SREEMTKNQVSLTCLVKGFYP SDIAV
VTHQGLSSPVTKSFNRGEC EWE SNGQPENNYKTTPPVLD SD
GSFFLY SKL TVD KSRWQQ GN
VFSCSVMHEALHNHYTQKSLSLSPGK
(SEQ ID NO: 218) (SEQ ID NO: 219) [hu anti- GAAATAGTGATGACGCAGTCT
CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
<huGIPR> CCAGCCACCCTGTCTGTGTCT
TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGGATTCA
2G10.607 CCAGGGGAAAGAGCCACCCT

VK3 (1-236) CTCCTGCAGGGCCAGTCAGAG
GGCGAGGGGCTGGAGTGGGTGGCAGCTATATGGTTTGATGC
VL]::huKLC NA
TGTTGATAGACACTTAGCCTG GTACGGTAAATACTATGCAGACGCCGTGAAGGGCCGATTCA
-CL + [hu GTACCAGCAGAAACCTGGCC
CCATCTCCAGAGACAACTCCAAGAACACGCTGTATCTGCAA
anti- AGGCTCCCAGGCTCCTCATCT
ATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTG
<huGIPR> ACGAAGCAGCCACCAGGGCC
TGCGAGAGATCAGACGATTTTTGGAGTGGTCCCCGACTACT oe oe 2G10.307 ACTGGTATCCCAGCCAGGGTC
GGGGCCAGGGAACCCTGGTCACCGTGTCTAGTGCCTCCACC
VH3 (1-472) AGTGGCAGTGGGTCTGGGAC
AAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAG
VH]::huIgG1 AGAGTTCACTCTCACCATCAG
CACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGG
zSEFL2-2 CAGCCTGCAGTCTGAAGATTT
ACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
(mAb); LMR TGCAGTTTATTACTGTCAGCA
GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
ID: SS- GTATAACCAGTGGCCTCTCAC
GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC

CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTG
GGAGATCAAACGAACGGTGG AATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTG
CTGCACCATCTGTCTTCATCTT AGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGC
CCCGCCATCTGATGAGCAGTT CCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTC
GAAATCTGGAACTGCCTCTGT CCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCC
TGTGTGCCTGCTGAATAACTT TGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACC
CTATCCCAGAGAGGCCAAAG CTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTG
TACAGTGGAAGGTGGATAAC CATAATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCA
GCCCTCCAATCGGGTAACTCC GCACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAG
CAGGAGAGTGTCACAGAGCA GACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCA
GGACAGCAAGGACAGCACCT ACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAA
ACAGCCTCAGCAGCACCCTGA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCC
CGCTGAGCAAAGCAGACTAC CCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTG
GAGAAACACAAAGTCTACGC ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGT
CTGCGAAGTCACCCATCAGGG GGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAG
CCTGAGCTCGCCCGTCACAAA ACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTC
GAGCTTCAACAGGGGAGAGT TATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGG
GT
GGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCAC
AACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAA
A
(SEQ ID NO: 220) (SEQ ID NO: 221) EIVMTQSPATLSVSPGERATLS QVQLVESGGGVVQPGRSLRLSCAASGFTFQNYGMHWVRQAP
CRASQSVDRHLAWYQQKPGQ GEGLEWVAAIWFDAYGKYYADAVKGRFTISRDNSKNTLYLQ
APRLLIYEAATRATGIPARVSGS MNSLRAEDTAVYYCARDQTIFGVVPDYWGQGTLVTVSSASTK
GSGTEFTLTISSLQSEDFAVYYC GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALT

AA QQYNQWPLTFGGGTKVEIKRT SGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN
VAAPSVFIFPPSDEQLKSGTASV TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
VCLLNNFYPREAKVQWKVDN MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCE
oe ALQSGNSQESVTEQDSKDSTYS EQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
LSSTLTLSKADYEKHKVYACE SKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAV
oe oe VTHQGLSSPVTKSFNRGEC
EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN
VFSCSVMHEALHNHYTQKSLSLSPGK
(SEQ ID NO: 222) (SEQ ID NO: 223) GAAATAGTGATGACGCAGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
CCAGCCACCCTGTCTGTGTCT TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGGATTCA
oe CCAGGGGAAAGAGCCACCCT CCTTCCAGAACTATGGCATGCACTGGGTCCGCCAGGCTCCA
CTCCTGCAGGGCCAGTCAGAG GGCGAGGGGCTGGAGTGGGTGGCAGCTATATGGTTTGATGC
TGTTAACCGGCACTTAGCCTG GTACGGTAAATACTATGCAGACGCCGTGAAGGGCCGATTCA
GTACCAGCAGAAACCTGGCC CCATCTCCAGAGACAACTCCAAGAACACGCTGTATCTGCAA
AGGCTCCCAGGCTCCTCATCT ATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTG
ACGAAGCAGCCACCAGGGCC TGCGAGAGATAAGACGATTTTTGGAGTGGTCCCCGACTACT
ACTGGTATCCCAGCCAGGTTC GGGGCCAGGGAACCCTGGTCACCGTGTCTAGTGCCTCCACC
[hu anti- AGTGGCAGTGGGTCTGGGAC
AAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAG
<huGIPR> AGAGTTCACTCTCACCATCAG
CACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGG
2G10.321 CAGCCTGCAGTCTGAAGATTT
ACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
VK3 (1-236) TGCAGTTTATTACTGTCAGCA
GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA p VL]::huKLC GTATAACCAGTGGCCTCTCAC
GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC
-CL + [hu TTTCGGCGGAGGGACCAAGGT
CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTG
anti- GGAGATCAAACGAACGGTGG
AATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTG
<huGIPR> NA CTGCACCATCTGTCTTCATCTT
AGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGC
2G10.321 CCCGCCATCTGATGAGCAGTT
CCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTC
VH3 (1-472) GAAATCTGGAACTGCCTCTGT
CCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCC
VH]::huIgG1 TGTGTGCCTGCTGAATAACTT
TGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACC
zSEFL2-2 CTATCCCAGAGAGGCCAAAG
CTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTG
(mAb); LMR TACAGTGGAAGGTGGATAAC
CATAATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCA
ID: SS- GCCCTCCAATCGGGTAACTCC
GCACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAG

GACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCA
GGACAGCAAGGACAGCACCT ACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAA
ACAGCCTCAGCAGCACCCTGA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCC
CGCTGAGCAAAGCAGACTAC CCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTG
GAGAAACACAAAGTCTACGC ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGT

CTGCGAAGTCACCCATCAGGG GGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAG
CCTGAGCTCGCCCGTCACAAA ACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTC
GAGCTTCAACAGGGGAGAGT TATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGG
oe GT
GGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCAC
AACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAA
oe cr oe A
(SEQ ID NO: 224) (SEQ ID NO: 225) EIVMTQSPATLSVSPGERATLS QVQLVESGGGVVQPGRSLRLSCAASGFTFQNYGMHWVRQAP

CRASQSVNRHLAWYQQKPGQ GEGLEWVAAIWFDAYGKYYADAVKGRFTISRDNSKNTLYLQ
APRLLIYEAATRATGIPARFSGS MNSLRAEDTAVYYCARDKTIFGVVPDYWGQGTLVTVSSASTK
oe GSGTEFTLTISSLQSEDFAVYYC GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALT
QQYNQWPLTFGGGTKVEIKRT SGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN
AA VAAPSVFIFPPSDEQLKSGTASV TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
VCLLNNFYPREAKVQWKVDN MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCE
ALQSGNSQESVTEQDSKDSTYS EQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
LSSTLTLSKADYEKHKVYACE SKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAV
VTHQGLSSPVTKSFNRGEC
EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN
VFSCSVMHEALHNHYTQKSLSLSPGK
(SEQ ID NO: 226) (SEQ ID NO: 227) GAAATAGTGATGACGCAGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
CCAGCCACCCTGTCTGTGTCT TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGGATTCA
p CCAGGGGAAAGAGCCACCCT CCTTCCAGAACTATGGCATGCACTGGGTCCGCCAGGCTCCA
CTCCTGCAGGGCCAGTCAGAG GGCGAGGGGCTGGAGTGGGTGGCAGCTATATGGTTTGATGC
[hu anti-<huGIPR> TGTTGAAAGACACTTAGCCTG
GTACGGTAAATACTATGCAGACGCCGTGAAGGGCCGATTCA
2G10.342 GTACCAGCAGAAACCTGGCC
CCATCTCCAGAGACAACTCCAAGAACACGCTGTATCTGCAA

AGGCTCCCAGGCTCCTCATCT ATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTG
( 1-236) VL ACGAAGCAGCCACCAGGGCC
TGCGAGAGATAAGACGATTTTTGGAGTGGTCCCCGACTACT
]
::huKLC
ACTGGTATCCCAGCCAGGTTC GGGGCCAGGGAACCCTGGTCACCGTGTCTAGTGCCTCCACC
-CL + [hu AGTGGCAGTGGGTCTGGGAC AAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAG
NA
anti-AGAGTTCACTCTCACCATCAG CACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGG
<huGIPR>
2G10.321 CAGCCTGCAGTCTGAAGATTT
ACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
VH3 1 472) TGCAGTTTATTACTGTCAGCA GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
- ( GTATCAGCAGTGGCCTCTCAC GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC
VH]::huIgG1 TTTCGGCGGAGGGACCAAGGT CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTG
zSEFL2-2 GGAGATCAAACGAACGGTGG AATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTG
(mAb); LMR
CTGCACCATCTGTCTTCATCTT AGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGC

ID: 26219 SS-CCCGCCATCTGATGAGCAGTT CCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTC
r,1 .7r GAAATCTGGAACTGCCTCTGT
CCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCC
TGTGTGCCTGCTGAATAACTT TGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACC
oe CTATCCCAGAGAGGCCAAAG CTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTG
TACAGTGGAAGGTGGATAAC CATAATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCA
oe cr oe GCCCTCCAATCGGGTAACTCC GCACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAG
CAGGAGAGTGTCACAGAGCA GACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCA
GGACAGCAAGGACAGCACCT ACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAA
ACAGCCTCAGCAGCACCCTGA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCC
CGCTGAGCAAAGCAGACTAC CCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTG
GAGAAACACAAAGTCTACGC ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGT
CTGCGAAGTCACCCATCAGGG GGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAG
CCTGAGCTCGCCCGTCACAAA ACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTC
GAGCTTCAACAGGGGAGAGT TATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGG
GT
GGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCAC
AACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAA
A
(SEQ ID NO: 228) (SEQ ID NO: 229) EIVMTQSPATLSVSPGERATLS QVQLVESGGGVVQPGRSLRLSCAASGFTFQNYGMHWVRQAP
CRASQSVERHLAWYQQKPGQ GEGLEWVAAIWFDAYGKYYADAVKGRFTISRDNSKNTLYLQ
APRLLIYEAATRATGIPARFSGS MNSLRAEDTAVYYCARDKTIFGVVPDYWGQGTLVTVSSASTK
GSGTEFTLTISSLQSEDFAVYYC GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALT
QQYQQWPLTFGGGTKVEIKRT SGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN
VAAPSVFIFPPSDEQLKSGTASV TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
AA
VCLLNNFYPREAKVQWKVDN MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCE
ALQSGNSQESVTEQDSKDSTYS EQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
LSSTLTLSKADYEKHKVYACE SKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAV
VTHQGLSSPVTKSFNRGEC
EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN
VFSCSVMHEALHNHYTQKSLSLSPGK
(SEQ ID NO: 230) (SEQ ID NO: 231) [hu anti- GAAATAGTGATGACGCAGTCT
CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
<huGIPR> CCAGCCACCCTGTCTGTGTCT
TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGGATTCA
2G10.316 CCAGGGGAAAGAGCCACCCT
CCTTCAGTAACTATGGCATGCACTGGGTCCGCCAGGCTCCA
VK3 (1-236) CTCCTGCAGGGCCAGTCAGAG
GGCGAGGGGCTGGAGTGGGTGGCAGCTATATGGTTTGATGC
VL]::huKLC TGTTTTCAGACACTTAGCCTG
GTACGGTAAATACTATGCAGACGCCGTGAAGGGCCGATTCA
-CL + [hu NA GTACCAGCAGAAACCTGGCC

anti- AGGCTCCCAGGCTCCTCATCT
ATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTG
<huGIPR> ACGAAGCAGCCACCAGGGCC
TGCGAGAGATAAGACGATTTTTGGAGTGGTCCCCGACTACT
re) 2G10.319 ACTGGTATCCCAGCCAGGTTC
GGGGCCAGGGAACCCTGGTCACCGTGTCTAGTGCCTCCACC
VH3 (1-472) AGTGGCAGTGGGTCTGGGAC
AAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAG
VH]::huIgG1 AGAGTTCACTCTCACCATCAG
CACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGG oe oe zSEFL2-2 CAGCCTGCAGTCTGAAGATTT
ACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
(mAb); LMR TGCAGTTTATTACTGTCAGCA
GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
ID: SS- GTATCAGAACTGGCCTCTCAC
GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC

CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTG
GGAGATCAAACGAACGGTGG AATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTG
CTGCACCATCTGTCTTCATCTT AGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGC
CCCGCCATCTGATGAGCAGTT CCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTC
GAAATCTGGAACTGCCTCTGT CCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCC
TGTGTGCCTGCTGAATAACTT TGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACC
CTATCCCAGAGAGGCCAAAG CTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTG
TACAGTGGAAGGTGGATAAC CATAATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCA
GCCCTCCAATCGGGTAACTCC GCACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAG
CAGGAGAGTGTCACAGAGCA GACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCA
GGACAGCAAGGACAGCACCT ACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAA
ACAGCCTCAGCAGCACCCTGA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCC
CGCTGAGCAAAGCAGACTAC CCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTG
GAGAAACACAAAGTCTACGC ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGT
CTGCGAAGTCACCCATCAGGG GGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAG
CCTGAGCTCGCCCGTCACAAA ACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTC
GAGCTTCAACAGGGGAGAGT TATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGG
GT
GGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCAC
AACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAA
A
(SEQ ID NO: 232) (SEQ ID NO: 233) EIVMTQSPATLSVSPGERATLS QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMHWVRQAP
CRASQSVFRHLAWYQQKPGQA GEGLEWVAAIWFDAYGKYYADAVKGRFTISRDNSKNTLYLQ
PRLLIYEAATRATGIPARFSGSG MNSLRAEDTAVYYCARDKTIFGVVPDYWGQGTLVTVSSASTK
SGTEFTLTISSLQSEDFAVYYCQ GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALT
QYQNWPLTFGGGTKVEIKRTV SGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN
AA AAPSVFIFPPSDEQLKSGTASVV TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
CLLNNFYPREAKVQWKVDNAL MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCE

QSGNSQESVTEQDSKDSTYSLS EQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
STLTLSKADYEKHKVYACEVT SKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAV
HQGLSSPVTKSFNRGEC
EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN
oe VFSCSVMHEALHNHYTQKSLSLSPGK
(SEQ ID NO: 234) (SEQ ID NO: 235) oe oe GAAATAGTGATGACGCAGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
CCAGCCACCCTGTCTGTGTCT TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGGATTCA
CCAGGGGAAAGAGCCACCCT CCTTCCAGAACTATGGCATGCACTGGGTCCGCCAGGCTCCA

CTCCTGCAGGGCCAGTCAGAG GGCGAGGGGCTGGAGTGGGTGGCAGCTATATGGTTTGATGC
o TGTTCTGAGTCACTTAGCCTG GTACGACAAATACTATGCAGACGCCGTGAAGGGCCGATTCA
oe GTACCAGCAGAAACCTGGCC CCATCTCCAGAGACAACTCCAAGAACACGCTGTATCTGCAA
c,.) AGGCTCCCAGGCTCCTCATCT ATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTG
o vo ACGAAGCAGCCACCAGGGCC TGCGAGAGATAAGTCGATTTTTGGAGTGGTCCCCGACTACT

ACTGGTATCCCAGCCAGGTTC GGGGCCAGGGAACCCTGGTCACCGTGTCTAGTGCCTCCACC
AGTGGCAGTGGGTCTGGGAC AAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAG
AGAGTTCACTCTCACCATCAG CACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGG
[hu anti-CAGCCTGCAGTCTGAAGATTT ACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
<huGIPR>
TGCAGTTTATTACTGTCAGCA GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
2G10.318 GTATAACAACTGGCCTCTCAC GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC
VK3 (1-236) TTTCGGCGGAGGGACCAAGGT CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTG
VL]::huKLC
GGAGATCAAACGAACGGTGG AATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTG
P
-CL + [hu CTGCACCATCTGTCTTCATCTT AGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGC
o anti-,D
NA CCCGCCATCTGATGAGCAGTT CCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTC
.
<huGIPR>
, GAAATCTGGAACTGCCTCTGT CCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCC
"
2G10.332 .
TGTGTGCCTGCTGAATAACTT TGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACC
"
,D
VH3 (1-472) , CTATCCCAGAGAGGCCAAAG CTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTG
' , VH]::huIgG1 , TACAGTGGAAGGTGGATAAC CATAATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCA
, zSEFL2-2 GCCCTCCAATCGGGTAACTCC GCACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAG
, (mAb); LMR
CAGGAGAGTGTCACAGAGCA GACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCA
ID: SS-GGACAGCAAGGACAGCACCT ACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAA

ACAGCCTCAGCAGCACCCTGA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCC
CGCTGAGCAAAGCAGACTAC CCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTG
GAGAAACACAAAGTCTACGC ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGT
CTGCGAAGTCACCCATCAGGG GGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAG
CCTGAGCTCGCCCGTCACAAA ACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTC

GAGCTTCAACAGGGGAGAGT TATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGG
n GT
GGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCAC
AACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAA
cp l=.) re) n A
_______________________________________________________________ o o oe Pi (SEQ ID NO: 236) (SEQ ID NO: 237) AA EIVMTQSPATLSVSPGERATLS QVQLVESGGGVVQPGRSLRLSCAASGFTFQNYGMHWVRQAP
oe c:
oe CRASQSVLSHLAWYQQKPGQA GEGLEWVAAIWFDAYDKYYADAVKGRFTISRDNSKNTLYLQ
PRLLIYEAATRATGIPARFSGSG MNSLRAEDTAVYYCARDKSIFGVVPDYWGQGTLVTVSSASTK
SGTEFTLTISSLQSEDFAVYYCQ GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALT
QYNNWPLTFGGGTKVEIKRTV SGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN
AAPSVFIFPPSDEQLKSGTASVV TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
CLLNNFYPREAKVQWKVDNAL MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCE
QSGNSQESVTEQDSKDSTYSLS EQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
STLTLSKADYEKHKVYACEVT SKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAV
HQGLSSPVTKSFNRGEC
EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN
VFSCSVMHEALHNHYTQKSLSLSPGK
(SEQ ID NO: 238) (SEQ ID NO: 239) GAAATAGTGATGACGCAGTCT CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
CCAGCCACCCTGTCTGTGTCT TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGGATTCA
CCAGGGGAAAGAGCCACCCT CCTTCCAGAACTATGGCATGCACTGGGTCCGCCAGGCTCCA
CTCCTGCAGGGCCAGTCAGAG GGCGAGGGGCTGGAGTGGGTGGCAGCTATATGGTTTGATGC
TGTTAACAGACACTTAGCCTG GTACGACAAATACTATGCAGACGCCGTGAAGGGCCGATTCA
[hu anti- GTACCAGCAGAAACCTGGCC
CCATCTCCAGAGACAACTCCAAGAACACGCTGTATCTGCAA
<huGIPR> AGGCTCCCAGGCTCCTCATCT
ATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTG
2G10.345 ACGAAGCAGCCACCAGGGCC
TGCGAGAGATAAGTCGATTTTTGGAGTGGTCCCCGACTACT
VK3 (1-236) ACTGGTATCCCAGCCAGGTTC
GGGGCCAGGGAACCCTGGTCACCGTGTCTAGTGCCTCCACC
VL]::huKLC AGTGGCAGTGGGTCTGGGAC
AAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAG
-CL + [hu AGAGTTCACTCTCACCATCAG
CACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGG
anti- CAGCCTGCAGTCTGAAGATTT
ACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
<huGIPR> NA TGCAGTTTATTACTGTCAGCA GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
2G10.332 GTATAACAACTGGCCTCTCAC
GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC
VH3 (1-472) TTTCGGCGGAGGGACCAAGGT
CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTG
VH]::huIgG1 GGAGATCAAACGAACGGTGG
AATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTG
zSEFL2-2 CTGCACCATCTGTCTTCATCTT
AGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGC
(mAb); LMR CCCGCCATCTGATGAGCAGTT
CCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTC
ID: SS- GAAATCTGGAACTGCCTCTGT
CCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCC

TGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACC

CTATCCCAGAGAGGCCAAAG CTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTG
.7r TACAGTGGAAGGTGGATAAC
CATAATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCA
GCCCTCCAATCGGGTAACTCC GCACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAG
oe CAGGAGAGTGTCACAGAGCA GACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCA
GGACAGCAAGGACAGCACCT ACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAA
oe oe ACAGCCTCAGCAGCACCCTGA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCC
CGCTGAGCAAAGCAGACTAC CCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTG
GAGAAACACAAAGTCTACGC ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGT
CTGCGAAGTCACCCATCAGGG GGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAG
CCTGAGCTCGCCCGTCACAAA ACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTC
GAGCTTCAACAGGGGAGAGT TATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGG
GT
GGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCAC
AACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAA
A
(SEQ ID NO: 240) (SEQ ID NO: 241) EIVMTQ SP ATL SVSPGERATLS QVQLVE SGGGVVQPGRSLRL SCAASGFTFQNYGMHWVRQAP
CRASQSVNRHLAWYQQKPGQ GEGLEWVAAIWFDAYDKYYADAVKGRFTISRDNSKNTLYLQ
APRLLIYEAATRATGIPARFSGS MNSLRAEDTAVYYCARDKSIFGVVPDYWGQGTLVTVSSASTK
GS GTEFTL TI S SLQSEDFAVYYC GP SVFPL AP S SKST S GGTAALGCLVKDYFPEPVTVSWN S GAL
T
QQYNNWPLTFGGGTKVEIKRT SGVHTFPAVLQS SGLY SLS SVVTVP S S SLGTQTYICNVNHKP SN
AA VAAPSVFIFPPSDEQLKSGTASV TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
VCLLNNFYPREAKVQWKVDN MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCE
ALQSGNSQESVTEQD SKD STY S EQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
L SSTLTL SKADYEKHKVYACE SKAKGQPREPQVYTLPP SREEMTKNQVSLTCLVKGFYP SDIAV
VTHQGLSSPVTKSFNRGEC EWE SNGQPENNYKTTPPVLD SD
GSFFLY SKL TVD KSRWQQ GN
VFSCSVMHEALHNHYTQKSLSLSPGK
(SEQ ID NO: 242) (SEQ ID NO: 243) [hu anti- GAAATAGTGATGACGCAGTCT
CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
<huGIPR> CCAGCCACCCTGTCTGTGTCT
TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGGATTCA
2G10.335 CCAGGGGAAAGAGCCACCCT
CCTTCCAGAACTATGGCATGCACTGGGTCCGCCAGGCTCCA
VK3 (1-236) CTCCTGCAGGGCCAGTCAGAG
GGCGAGGGGCTGGAGTGGGTGGCAGCTATATGGTTTGATGC
VL]::huKLC TGTTACCAGCCACTTAGCCTG
GTACGACAAATACTATGCAGACGCCGTGAAGGGCCGATTCA
-CL + [hu GTACCAGCAGAAACCTGGCC
CCATCTCCAGAGACAACTCCAAGAACACGCTGTATCTGCAA
anti- NA AGGCTCCCAGGCTCCTCATCT
ATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTG
<huGIPR> ACGAAGCAGCCACCAGGGCC
TGCGAGAGATCTCGCGATTTTTGGAGTGGTCCCCGACTACT
2G10.335 ACTGGTATCCCAGCCAGGTTC

VH3 (1-472) AGTGGCAGTGGGTCTGGGAC
AAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAG
VH]::huIgG1 AGAGTTCACTCTCACCATCAG
CACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGG
re) ACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
(mAb); LMR TGCAGTTTATTACTGTCAGCA
GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
ID: SS- GTATAACCAGTGGCCTCTCAC
GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC oe oe CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTG
GGAGATCAAACGAACGGTGG AATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTG
CTGCACCATCTGTCTTCATCTT AGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGC

CCCGCCATCTGATGAGCAGTT CCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTC
n.) o GAAATCTGGAACTGCCTCTGT CCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCC
oe i-J
TGTGTGCCTGCTGAATAACTT TGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACC
c,.) --.1 CTATCCCAGAGAGGCCAAAG CTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTG
o vo TACAGTGGAAGGTGGATAAC CATAATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCA
--.1 GCCCTCCAATCGGGTAACTCC GCACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAG
CAGGAGAGTGTCACAGAGCA GACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCA
GGACAGCAAGGACAGCACCT ACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAA
ACAGCCTCAGCAGCACCCTGA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCC
CGCTGAGCAAAGCAGACTAC CCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTG
GAGAAACACAAAGTCTACGC ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGT
CTGCGAAGTCACCCATCAGGG GGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAG
CCTGAGCTCGCCCGTCACAAA ACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTC
P
GAGCTTCAACAGGGGAGAGT TATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGG
o GT
GGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCAC .
AACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAA
, '.
A
"
, (SEQ ID NO: 244) (SEQ ID NO: 245) ' , , EIVMTQSPATLSVSPGERATLS QVQLVESGGGVVQPGRSLRLSCAASGFTFQNYGMHWVRQAP
.
, CRASQSVTSHLAWYQQKPGQA GEGLEWVAAIWFDAYDKYYADAVKGRFTISRDNSKNTLYLQ
, PRLLIYEAATRATGIPARFSGSG MNSLRAEDTAVYYCARDLAIFGVVPDYWGQGTLVTVSSASTK
SGTEFTLTISSLQSEDFAVYYCQ GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALT
QYNQWPLTFGGGTKVEIKRTV SGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN
AA AAPSVFIFPPSDEQLKSGTASVV TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
CLLNNFYPREAKVQWKVDNAL MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCE
QSGNSQESVTEQDSKDSTYSLS EQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
STLTLSKADYEKHKVYACEVT SKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAV

HQGLSSPVTKSFNRGEC
EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN n VFSCSVMHEALHNHYTQKSLSLSPGK
cp (SEQ ID NO: 246) (SEQ ID NO: 247) n.) o c: [hu anti- GAAATAGTGATGACGCAGTCT
CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
oe ,c1 <huGIPR> NA CCAGCCACCCTGTCTGTGTCT
TGGGAGGTCCCTGAGACTCTCCTGTGCAGCATCTGGATTCA 'a 2G10.330 CCAGGGGAAAGAGCCACCCT
CCTTCCAGAACTATGGCATGCACTGGGTCCGCCAGGCTCCA oe c:
oe VK3 (1-236) CTCCTGCAGGGCCAGTCAGAG
GGCGAGGGGCTGGAGTGGGTGGCAGCTATATGGTTTGATGC
VL]::huKLC TGTTGATCAGCACTTAGCCTG
GGCTTTCAAATACTATGCAGACGCCGTGAAGGGCCGATTCA
-CL + [hu GTACCAGCAGAAACCTGGCC
CCATCTCCAGAGACAACTCCAAGAACACGCTGTATCTGCAA
anti- AGGCTCCCAGGCTCCTCATCT
ATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTG
<huGIPR> ACCAGGCAGCCACCAGGGCC
TGCGAGAGATCTCGCGATTTTTGGAGTGGTCCCCGACTACT
2G10.330 ACTGGTATCCCAGCCAGGTTC
GGGGCCAGGGAACCCTGGTCACCGTGTCTAGTGCCTCCACC
VH3 (1-472) AGTGGCAGTGGGTCTGGGAC
AAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAG
VH]::huIgG1 AGAGTTCACTCTCACCATCAG
CACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGG
zSEFL2-2 CAGCCTGCAGTCTGAAGATTT
ACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
(mAb); LMR TGCAGTTTATTACTGTCAGCA
GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
ID: SS- GTATCAGAACTGGCCTCTCAC
GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC

CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTG
GGAGATCAAACGAACGGTGG AATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTG
CTGCACCATCTGTCTTCATCTT AGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGC
CCCGCCATCTGATGAGCAGTT CCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTC
GAAATCTGGAACTGCCTCTGT CCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCC
TGTGTGCCTGCTGAATAACTT TGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACC
CTATCCCAGAGAGGCCAAAG CTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTG
TACAGTGGAAGGTGGATAAC CATAATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCA
GCCCTCCAATCGGGTAACTCC GCACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAG
CAGGAGAGTGTCACAGAGCA GACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCA
GGACAGCAAGGACAGCACCT ACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAA
ACAGCCTCAGCAGCACCCTGA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCC
CGCTGAGCAAAGCAGACTAC CCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTG
GAGAAACACAAAGTCTACGC ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGT
CTGCGAAGTCACCCATCAGGG GGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAG
CCTGAGCTCGCCCGTCACAAA ACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTC
GAGCTTCAACAGGGGAGAGT TATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGG
GT
GGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCAC
AACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAA
A

(SEQ ID NO: 248) (SEQ ID NO: 249) EIVMTQSPATLSVSPGERATLS QVQLVESGGGVVQPGRSLRLSCAASGFTFQNYGMHWVRQAP
AA
CRASQSVDQHLAWYQQKPGQ GEGLEWVAAIWFDAAFKYYADAVKGRFTISRDNSKNTLYLQ
oe APRLLIYQAATRATGIPARFSGS MNSLRAEDTAVYYCARDLAIFGVVPDYWGQGTLVTVSSASTK
GSGTEFTLTISSLQSEDFAVYYC GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALT
oe oe QQYQNWPLTFGGGTKVEIKRT SGVHTFPAVLQSSGLY SLSSVVTVP SSSLGTQTYICNVNHKP SN
VAAPSVFIFPPSDEQLKSGTASV TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
VCLLNNFYPREAKVQWKVDN MI SRTPEVTCVVVDVSHEDPEVKFNWYVD GVEVHNAKTKPCE

ALQSGNSQESVTEQDSKDSTYS EQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
n.) o L SSTLTL SKADYEKHKVYACE SKAKGQPREPQVYTLPP SREEMTKNQVSLTCLVKGFYP SDIAV
oe i-J
VTHQGLSSPVTKSFNRGEC
EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN c,.) --.1 VFSCSVMHEALHNHYTQKSLSLSPGK
o (SEQ ID NO: 250) (SEQ ID NO: 251) --.1 ATGGACATGAGGGTGCCCGCT ATGGACATGAGGGTGCCCGCTCAGCTCCTGGGGCTCCTGCT
CAGCTCCTGGGGCTCCTGCTG GCTGTGGCTGAGAGGTGCGCGCTGTCAGGTGCAGCTGGTGG
CTGTGGCTGAGAGGTGCGCGC AGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGA
TGTGAAATCGTGATGACGCAG CTCTCCTGTGCAGCATCTGGATTCACCTTCAGTAACTATGGC
TCTCCAGCCACCCTGTCTGTG ATGCACTGGGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTG
TCTCCAGGGGAAAGAGCCAC GGTGGCAGCTATCTGGTTTGATGCAAGTGATAAATACTATG
CCTCTCCTGCAGGGCCAGTCA CAGACGCCGTGAAGGGCCGATTCACCATCTCCAGAGACAAC
GAGTGTTAGCGAACACTTAGC TCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGC
P
CTGGTACCAGCAGAAACCTG CGAGGACACGGCTGTGTATTACTGTGCGAGAGATCTGGCGA

L.
GCCAGGCTCCCAGGCTCCTCA TTTTTGGAGTGATTCCCGACTACTGGGGCCAGGGAACCCTG
.
, TCTACGAAGCAGCCACCAGG GTCACCGTGTCTAGTGCCTCCACCAAGGGCCCATCGGTCTTC
..
GCCACTGGTATCCCAGCCAGG CCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGC
,-i Go TTCAGTGGCAGTGGGTCTGGG
GGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGG
Lo':
re) r TGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTG .
, e'l NA
L.
in AGCAGCCTGCAGTCTGAAGAT
CACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCC , ci3 0.0 TTTGCAGTTTATTACTGTCAG
CTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCAC
¨
CAGTATCAGAACTGGCCTCTC CCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACA
ACTTTCGGCGGAGGGACCAA CCAAGGTGGACAAGAAAGTTGAGCCCAAATCTTGTGACAAA
GGTGGAGATCAAACGAACGG ACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGG
TGGCTGCACCATCTGTCTTCA GGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACA
TCTTCCCGCCATCTGATGAGC CCCTCTACATCACCCGGGAGCCTGAGGTCACATGCGTGGTG
AGTTGAAATCTGGAACTGCCT GTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTG

CTGTTGTGTGCCTGCTGAATA GTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAG
n ACTTCTATCCCAGAGAGGCCA CCGTGCGAGGAGCAGTACGGCAGCACGTACCGTTGCGTCAG
cp AAGTACAGTGGAAGGTGGAT CGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGG
n.) o AACGCCCTCCAATCGGGTAAC AGTACAAGTGCAAGGTGTCCAACAAAGCCCTCCCAGCCCCC
oe TCCCAGGAGAGTGTCACAGA ATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAG
'a GCAGGACAGCAAGGACAGCA AACCACAGGTGTACACCCTGCCCCCATCCCGGGAGGAGATG
oe cA
oe CCTACAGCCTCAGCAGCACCC ACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTT
TGACGCTGAGCAAAGCAGAC CTATCCCAGCGATATCGCCGTGGAGTGGGAGAGCAATGGGC
TACGAGAAACACAAAGTCTA AGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGAC

n.) CGCCTGCGAAGTCACCCATCA TCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGAC
o GGGCCTGAGCTCGCCCGTCAC AAGAGTAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGT
oe i-J
AAAGAGCTTCAACAGGGGAG GATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCC
c,.) --.1 AGTGT TCTCCCTGTCTCCGGGTAAA
o o (SEQ ID NO: 1361 (SEQ ID NO: 1362 --.1 EIVMTQSPATL SVSPGERATLS QVQLVE SGGGVVQPGRSLRL SCAASGFTFSNYGMHWVRQAP
CRASQSVSEHLAWYQQKPGQA GEGLEWVAAIWFDASDKYYADAVKGRFTISRDNSKNTLYLQ
PRLLIYEAATRATGIPARFSGSG MNSLRAEDTAVYYCARDLAIFGVIPDYWGQGTLVTVSSASTK
SGTEFTLTISSLQSEDFAVYYCQ GP SVFPL AP S SKST S GGTAALGCLVKDYFPEPVTVSWN S GAL T
QYQNWPLTFGGGTKVEIKRTV SGVHTFPAVLQSSGLY SLSSVVTVP SSSLGTQTYICNVNHKP SN
AA AAPSVFIFPPSDEQLKSGTASVV TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLY
CLLNNFYPREAKVQWKVDNAL ITREPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEE
QSGNSQESVTEQD SKD STY SL S QYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTIS
p STLTLSKADYEKHKVYACEVT KAKGQPREPQVYTLPP SREEMTKNQVSLTCLVKGFYPSDIAVE

L.
HQGL SSPVTKSFNRGEC
WESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNV .
, FSCSVMHEALHNHYTQKSLSLSPGK
..
(SEQ ID NO: 1288) (SEQ ID NO: 1289) , ATGGACATGAGGGTGCCCGCT ATGGACATGAGGGTGCCCGCTCAGCTCCTGGGGCTCCTGCT
.
, , CAGCTCCTGGGGCTCCTGCTG GCTGTGGCTGAGAGGTGCGCGCTGTCAGGTGCAGCTGGTGG
.
, L.
, CTGTGGCTGAGAGGTGCGCGC AGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGA
TGTGAAATCGTGATGACGCAG CTCTCCTGTGCAGCATCTGGATTCACCTTCAGTAACTATGGC
TCTCCAGCCACCCTGTCTGTG ATGCACTGGGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTG
TCTCCAGGGGAAAGAGCCAC GGTGGCAGCTATCTGGTTTGATGCAAGTGATAAATACTATG
c-1 oe CCTCTCCTGCAGGGCCAGTCA
CAGACGCCGTGAAGGGCCGATTCACCATCTCCAGAGACAAC
re) TCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGC
in CTGGTACCAGCAGAAACCTG
CGAGGACACGGCTGTGTATTACTGTGCGAGAGATATTGCGA
ci3 0.0 GCCAGGCTCCCAGGCTCCTCA

-n TCTATGGTGCAGCCACCAGGG GTCACCGTGTCTAGTGCCTCCACCAAGGGCCCATCGGTCTTC

CCACTGGTATCCCAGCCAGGT CCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGC
cp TCAGTGGCAGTGGGTCTGGGA GGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGG
n.) o CAGAGTTCACTCTCACCATCA TGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTG
oe GCAGCCTGCAGTCTGAAGATT CACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCC
'a TTGCAGTTTATTACTGTCAGC CTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCAC
oe cA
oe AGTATAATAACTGGCCTCTCA CCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACA
CTTTCGGCGGAGGGACCAAG CCAAGGTGGACAAGAAAGTTGAGCCCAAATCTTGTGACAAA
GTGGAGATCAAACGAACGGT ACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGG

n.) GGCTGCACCATCTGTCTTCAT GGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACA
o CTTCCCGCCATCTGATGAGCA CCCTCTACATCACCCGGGAGCCTGAGGTCACATGCGTGGTG
oe i-J
GTTGAAATCTGGAACTGCCTC GTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTG
c,.) --.1 TGTTGTGTGCCTGCTGAATAA GTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAG
o o CTTCTATCCCAGAGAGGCCAA CCGTGCGAGGAGCAGTACGGCAGCACGTACCGTTGCGTCAG
--.1 AGTACAGTGGAAGGTGGATA CGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGG
ACGCCCTCCAATCGGGTAACT AGTACAAGTGCAAGGTGTCCAACAAAGCCCTCCCAGCCCCC
CCCAGGAGAGTGTCACAGAG ATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAG
CAGGACAGCAAGGACAGCAC AACCACAGGTGTACACCCTGCCCCCATCCCGGGAGGAGATG
CTACAGCCTCAGCAGCACCCT ACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTT
GACGCTGAGCAAAGCAGACT CTATCCCAGCGATATCGCCGTGGAGTGGGAGAGCAATGGGC
ACGAGAAACACAAAGTCTAC AGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGAC
GCCTGCGAAGTCACCCATCAG TCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGAC
P
GGCCTGAGCTCGCCCGTCACA AAGAGTAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGT
o L.
AAGAGCTTCAACAGGGGAGA GATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCC
.
, GTGT TCTCCCTGTCTCCGGGTAAA
' (SEQ ID NO: 1363 (SEQ ID NO: 1364 , EIVMTQ SP ATL SVSPGERATLS QVQLVE SGGGVVQPGRSLRL SCAASGFTFSNYGMHWVRQAP
L.
, , CRASQSVSSNLAWYQQKPGQA GEGLEWVAAIWFDASDKYYADAVKGRFTISRDNSKNTLYLQ
.
, L.
PRLLIYGAATRATGIPARFSGSG MNSLRAEDTAVYYCARDIAIFGVVPDYWGQGTLVTVSSASTK
, SGTEFTLTIS SLQSEDFAVYYCQ GP SVFPL AP S SKST S GGTAALGCLVKDYFPEPVTVSWN S GAL T
QYNNWPLTFGGGTKVEIKRTV SGVHTFPAVLQS SGLY SLS SVVTVP S S SLGTQTYICNVNHKP SN
AA AAPSVFIFPPSDEQLKSGTASVV TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLY
CLLNNFYPREAKVQWKVDNAL ITREPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEE
QSGNSQESVTEQD SKD STY SL S QYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTIS
STLTLSKADYEKHKVYACEVT KAKGQPREPQVYTLPP SREEMTKNQVSLTCLVKGFYPSDIAVE
HQGL S SPVTKSFNRGEC WE SNGQPENNYKTTPPVLD SD GSFFLY

n FSCSVMHEALHNHYTQKSLSLSPGK

(SEQ ID NO: 1299) (SEQ ID NO: 1300) cp o ATGGACATGAGGGTGCCCGCT
ATGGACATGAGGGTGCCCGCTCAGCTCCTGGGGCTCCTGCT n.) o in r- CAGCTCCTGGGGCTCCTGCTG
GCTGTGGCTGAGAGGTGCGCGCTGTCAGGTGCAGCTGGTGG oe ci3 ci NA
CTGTGGCTGAGAGGTGCGCGC AGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGA
'a ¨
TGTGAAATCGTGCTGACGCAG CTCTCCTGTGCAGCATCTGGATTCACCTTCAGTAACTATGGC
oe cA
oe TCTCCAGCCACCCTGTCTCTG ATGCACTGGGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTG
TCTCCAGGGGAAAGAGCCAC GGTGGCAGCTATCTGGTTTGATGCAAGTGATAAATACTATG
CCTCTCCTGCAGGGCCAGTCA CAGACGCCGTGAAGGGCCGATTCACCATCTCCAGAGACAAC

t..) GAGTGTTAGCAGCAACTTAGC TCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGC
o CTGGTACCAGCAGAAACCTG CGAGGACACGGCTGTGTATTACTGTGCGAGAGATCAGGCGA
oe GCCAGGCTCCCAGGCTCCTCA TTTTTGGAGTGGTCCCCGATTACTGGGGCCAGGGAACCCTG
c,.) --.1 TCTATGGTGCAGCCACCAGGG GTCACCGTGTCTAGTGCCTCCACCAAGGGCCCATCGGTCTTC
o o CCACTGGTATCCCAGACAGGT CCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGC
--.1 TCAGTGGCAGTGGGTCTGGGA GGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGG
CAGAGTTCACTCTCACCATCA TGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTG
GCAGGCTGGAGCCTGAAGATT CACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCC
TTGCAGTTTATTACTGTCAGC CTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCAC
AGTATAATAACTGGCCTCTCA CCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACA
CTTTCGGCGGAGGGACCAAG CCAAGGTGGACAAGAAAGTTGAGCCCAAATCTTGTGACAAA
GTGGAGATCAAACGAACGGT ACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGG
GGCTGCACCATCTGTCTTCAT GGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACA
P
CTTCCCGCCATCTGATGAGCA CCCTCTACATCACCCGGGAGCCTGAGGTCACATGCGTGGTG
o L.
GTTGAAATCTGGAACTGCCTC GTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTG
.
, TGTTGTGTGCCTGCTGAATAA GTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAG
' CTTCTATCCCAGAGAGGCCAA CCGTGCGAGGAGCAGTACGGCAGCACGTACCGTTGCGTCAG
" AGTACAGTGGAAGGTGGATA
CGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGG Lo':
, ACGCCCTCCAATCGGGTAACT AGTACAAGTGCAAGGTGTCCAACAAAGCCCTCCCAGCCCCC
.
, L.
CCCAGGAGAGTGTCACAGAG ATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAG
, CAGGACAGCAAGGACAGCAC AACCACAGGTGTACACCCTGCCCCCATCCCGGGAGGAGATG
CTACAGCCTCAGCAGCACCCT ACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTT
GACGCTGAGCAAAGCAGACT CTATCCCAGCGATATCGCCGTGGAGTGGGAGAGCAATGGGC
ACGAGAAACACAAAGTCTAC AGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGAC
GCCTGCGAAGTCACCCATCAG TCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGAC
GGCCTGAGCTCGCCCGTCACA AAGAGTAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGT
AAGAGCTTCAACAGGGGAGA GATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCC

GTGT TCTCCCTGTCTCCGGGTAAA
n (SEQ ID NO: 1365 (SEQ ID NO: 1366 cp EIVLTQSPATLSLSPGERATLSC QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMHWVRQAP
t..) o AA
RASQSVSSNLAWYQQKPGQAP GEGLEWVAAIWFDASDKYYADAVKGRFTISRDNSKNTLYLQ
oe RLLIYGAATRATGIPDRFSGSGS MNSLRAEDTAVYYCARDQAIFGVVPDYWGQGTLVTVSSASTK
GTEFTLTISRLEPEDFAVYYCQ GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALT
oe cA
oe QYNNWPLTFGGGTKVEIKRTV SGVHTFPAVLQSSGLY SLSSVVTVP SSSLGTQTYICNVNHKP SN
AAPSVFIFPPSDEQLKSGTASVV TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLY
CLLNNFYPREAKVQWKVDNAL ITREPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEE

n.) QSGNSQESVTEQD SKD STY SL S QYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTIS
o STLTLSKADYEKHKVYACEVT KAKGQPREPQVYTLPP SREEMTKNQVSLTCLVKGFYPSDIAVE
oe i-J
HQGL SSPVTKSFNRGEC WE SNGQPENNYKTTPPVLD SD GSFFLY
SKL TVDKSRWQQGNV c,.) --.1 F SC SVMHEALHNHYTQKSL SL SP GK
o o (SEQ ID NO: 1309) (SEQ ID NO: 1310) --.1 ATGGACATGAGGGTGCCCGCT ATGGACATGAGGGTGCCCGCTCAGCTCCTGGGGCTCCTGCT
CAGCTCCTGGGGCTCCTGCTG GCTGTGGCTGAGAGGTGCGCGCTGTCAGGTGCAGCTGGTGG
CTGTGGCTGAGAGGTGCGCGC AGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGA
TGTGAAATCGTGCTGACGCAG CTCTCCTGTGCAGCATCTGGATTCACCTTCAGTAACTATGGC
TCTCCAGCCACCCTGTCTCTG ATGCACTGGGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTG
TCTCCAGGGGAAAGAGCCAC GGTGGCAGCTATCTGGTTTGATGCAAGTGATAAATACTATG
CCTCTCCTGCAGGGCCAGTCA CAGACGCCGTGAAGGGCCGATTCACCATCTCCAGAGACAAC
GAGTGTTAGCGAACACTTAGC TCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGC
p CTGGTACCAGCAGAAACCTG CGAGGACACGGCTGTGTATTACTGTGCGAGAGATCTGGCGA

L.
GCCAGGCTCCCAGGCTCCTCA TTTTTGGAGTGATTCCCGACTACTGGGGCCAGGGAACCCTG
.
, TCTACGAAGCAGCCACCAGG GTCACCGTGTCTAGTGCCTCCACCAAGGGCCCATCGGTCTTC
..
GCCACTGGTATCCCAGACAGG CCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGC
o , o TTCAGTGGCAGTGGGTCTGGG
GGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGG L.
, re) r TGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTG
.
, L.
in AGCAGGCTGGAGCCTGAAGA
CACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCC
, ci3 0.0 TTTTGCAGTTTATTACTGTCAG
CTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCAC
¨
CAGTATCAGAACTGGCCTCTC CCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACA
ACTTTCGGCGGAGGGACCAA CCAAGGTGGACAAGAAAGTTGAGCCCAAATCTTGTGACAAA
GGTGGAGATCAAACGAACGG ACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGG
TGGCTGCACCATCTGTCTTCA GGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACA
TCTTCCCGCCATCTGATGAGC CCCTCTACATCACCCGGGAGCCTGAGGTCACATGCGTGGTG
AGTTGAAATCTGGAACTGCCT GTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTG

CTGTTGTGTGCCTGCTGAATA GTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAG
n ACTTCTATCCCAGAGAGGCCA CCGTGCGAGGAGCAGTACGGCAGCACGTACCGTTGCGTCAG
cp AAGTACAGTGGAAGGTGGAT CGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGG
n.) o AACGCCCTCCAATCGGGTAAC AGTACAAGTGCAAGGTGTCCAACAAAGCCCTCCCAGCCCCC
oe TCCCAGGAGAGTGTCACAGA ATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAG
'a GCAGGACAGCAAGGACAGCA AACCACAGGTGTACACCCTGCCCCCATCCCGGGAGGAGATG
oe cA
oe CCTACAGCCTCAGCAGCACCC ACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTT
TGACGCTGAGCAAAGCAGAC CTATCCCAGCGATATCGCCGTGGAGTGGGAGAGCAATGGGC
TACGAGAAACACAAAGTCTA AGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGAC

n.) CGCCTGCGAAGTCACCCATCA TCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGAC
=
GGGCCTGAGCTCGCCCGTCAC AAGAGTAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGT
oe i-J
AAAGAGCTTCAACAGGGGAG GATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCC
c,.) --.1 AGTGT TCTCCCTGTCTCCGGGTAAA
o o (SEQ ID NO: 1367 (SEQ ID NO: 1368 --.1 EIVLTQ SPATLSL SP GERATL SC QVQLVE SGGGVVQPGRSLRL SCAASGFTFSNYGMHWVRQAP
RASQSVSEHLAWYQQKPGQAP GEGLEWVAAIWFDASDKYYADAVKGRFTISRDNSKNTLYLQ
RLLIYEAATRATGIPD RF S GS GS MN SLRAEDTAVYYCARDLAIFGVIPDYWGQGTLVTVS SASTK
GTEFTLTISRLEPEDFAVYYCQ GP SVFPL AP S SKST S GGTAALGCLVKDYFPEPVTVSWN S GAL T
QYQNWPLTFGGGTKVEIKRTV SGVHTFPAVLQS SGLY SLS SVVTVP S S SLGTQTYICNVNHKP SN
AA AAPSVFIFPPSDEQLKSGTASVV TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLY
CLLNNFYPREAKVQWKVDNAL ITREPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEE
QSGNSQESVTEQD SKD STY SL S QYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTIS
p STLTLSKADYEKHKVYACEVT KAKGQPREPQVYTLPP SREEMTKNQVSLTCLVKGFYPSDIAVE

L.
HQGL S SPVTKSFNRGEC WE SNGQPENNYKTTPPVLD SD GSFFLY
SKL TVDKSRWQQGNV .
, FSCSVMHEALHNHYTQKSLSLSPGK
..
(SEQ ID NO: 1319) (SEQ ID NO: 1320) , L.
, , .
, L.
, n ,-i cp w =
oe 'a oe cA
oe ATGGACATGAGGGTGCCCGCT ATGGACATGAGGGTGCCCGCTCAGCTCCTGGGGCTCCTGCT
CAGCTCCTGGGGCTCCTGCTG GCTGTGGCTGAGAGGTGCGCGCTGTCAGGTGCAGCTGGTGG
CTGTGGCTGAGAGGTGCGCGC AGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGA

t..) TGTGAAATCGTGCTGACGCAG CTCTCCTGTGCAGCATCTGGATTCACCTTCAGTAACTATGGC
o TCTCCAGCCACCCTGTCTCTG ATGCACTGGGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTG
oe TCTCCAGGGGAAAGAGCCAC GGTGGCAGCTATCTGGTTTGATGCAAGTGATAAATACTATG
c,.) --.1 CCTCTCCTGCAGGGCCAGTCA CAGACGCCGTGAAGGGCCGATTCACCATCTCCAGAGACAAC
o GAGTGTTAGCAGCAACTTAGC TCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGC
--.1 CTGGTACCAGCAGAAACCTG CGAGGACACGGCTGTGTATTACTGTGCGAGAGATATTGCGA
GCCAGGCTCCCAGGCTCCTCA TTTTTGGAGTGGTCCCCGACTACTGGGGCCAGGGAACCCTG
TCTATGGTGCAGCCACCAGGG GTCACCGTGTCTAGTGCCTCCACCAAGGGCCCATCGGTCTTC
CCACTGGTATCCCAGACAGGT CCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGC
TCAGTGGCAGTGGGTCTGGGA GGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGG
CAGAGTTCACTCTCACCATCA TGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTG
GCAGGCTGGAGCCTGAAGATT CACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCC
TTGCAGTTTATTACTGTCAGC CTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCAC
P
o o AGTATAATAACTGGCCTCTCA
CCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACA o 7r L.
NA CTTTCGGCGGAGGGACCAAG CCAAGGTGGACAAGAAAGTTGAGCCCAAATCTTGTGACAAA
.
, in GTGGAGATCAAACGAACGGT
ACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGG ' ci3 .
0.0 GGCTGCACCATCTGTCTTCAT
GGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACA " --CTTCCCGCCATCTGATGAGCA CCCTCTACATCACCCGGGAGCCTGAGGTCACATGCGTGGTG
Lo':
, GTTGAAATCTGGAACTGCCTC GTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTG
.
, L.
TGTTGTGTGCCTGCTGAATAA GTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAG
, CTTCTATCCCAGAGAGGCCAA CCGTGCGAGGAGCAGTACGGCAGCACGTACCGTTGCGTCAG
AGTACAGTGGAAGGTGGATA CGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGG
ACGCCCTCCAATCGGGTAACT AGTACAAGTGCAAGGTGTCCAACAAAGCCCTCCCAGCCCCC
CCCAGGAGAGTGTCACAGAG ATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAG
CAGGACAGCAAGGACAGCAC AACCACAGGTGTACACCCTGCCCCCATCCCGGGAGGAGATG
CTACAGCCTCAGCAGCACCCT ACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTT
GACGCTGAGCAAAGCAGACT CTATCCCAGCGATATCGCCGTGGAGTGGGAGAGCAATGGGC

ACGAGAAACACAAAGTCTAC AGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGAC
n ,-i GCCTGCGAAGTCACCCATCAG TCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGAC
GGCCTGAGCTCGCCCGTCACA AAGAGTAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGT
ci) r.) o AAGAGCTTCAACAGGGGAGA GATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCC
oe GTGT TCTCCCTGTCTCCGGGTAAA
(SEQ ID NO: 1369 (SEQ ID NO: 1370 oe cA
oe EIVLTQ SPATLSL SP GERATL SC QVQLVE SGGGVVQPGRSLRL SCAASGFTFSNYGMHWVRQAP
RASQSVSSNLAWYQQKPGQAP GEGLEWVAAIWFDASDKYYADAVKGRFTISRDNSKNTLYLQ
RLLIYGAATRATGIPDRFSGSGS MNSLRAEDTAVYYCARDIAIFGVVPDYWGQGTLVTVSSASTK

n.) GTEFTLTISRLEPEDFAVYYCQ GP SVFPL AP S SKST S GGTAALGCLVKDYFPEPVTVSWN S GAL T
o QYNNWPLTFGGGTKVEIKRTV SGVHTFPAVLQSSGLY SLSSVVTVP SSSLGTQTYICNVNHKP SN
oe i-J
AA AAPSVFIFPPSDEQLKSGTASVV TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLY
c,.) --.1 CLLNNFYPREAKVQWKVDNAL ITREPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEE
o o QSGNSQESVTEQD SKD STY SL S QYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTIS
--.1 STLTLSKADYEKHKVYACEVT KAKGQPREPQVYTLPP SREEMTKNQVSLTCLVKGFYPSDIAVE
HQGL SSPVTKSFNRGEC WE SNGQPENNYKTTPPVLD SD GSFFLY
SKL TVDKSRWQQGNV
FSCSVMHEALHNHYTQKSLSLSPGK
(SEQ ID NO: 1329) (SEQ ID NO: 1230) ATGGACATGAGGGTGCCCGCT ATGGACATGAGGGTGCCCGCTCAGCTCCTGGGGCTCCTGCT
CAGCTCCTGGGGCTCCTGCTG GCTGTGGCTGAGAGGTGCGCGCTGTCAGGTGCAGCTGGTGG
CTGTGGCTGAGAGGTGCGCGC AGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGA
TGTGAAATCGTGCTGACGCAG CTCTCCTGTGCAGCATCTGGATTCACCTTCAGTAACTATGGC
p TCTCCAGCCACCCTGTCTCTG ATGCACTGGGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTG

L.
TCTCCAGGGGAAAGAGCCAC GGTGGCAGCTATCTGGTTTGATGCAAGTGATAAATACTATG
.
, CCTCTCCTGCAGGGCCAGTCA CAGACGCCGTGAAGGGCCGATTCACCATCTCCAGAGACAAC
..
GAGTGTTGATCTGCACTTAGC TCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGC
, CTGGTACCAGCAGAAACCTG CGAGGACACGGCTGTGTATTACTGTGCGAGAGATTTGGCGA
L.
, , GCCAGGCTCCCAGGCTCCTCA TTTTTGGAGTGGTCCCCGACTACTGGGGCCAGGGAACCCTG
.
, o TCTACGAAGCAGCCACCAGG
GTCACCGTGTCTAGTGCCTCCACCAAGGGCCCATCGGTCTTC , .7r re) CCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGC
NA
in TTCAGTGGCAGTGGGTCTGGG
GGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGG
ci3 ACAGAGTTCACTCTCACCATC
TGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTG
0.0 ¨
AGCAGGCTGGAGCCTGAAGA CACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCC
TTTTGCAGTTTATTACTGTCAG CTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCAC
CAGTATCAGAACTGGCCTCTC CCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACA
ACTTTCGGCGGAGGGACCAA CCAAGGTGGACAAGAAAGTTGAGCCCAAATCTTGTGACAAA

GGTGGAGATCAAACGAACGG ACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGG
n TGGCTGCACCATCTGTCTTCA GGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACA
cp TCTTCCCGCCATCTGATGAGC CCCTCTACATCACCCGGGAGCCTGAGGTCACATGCGTGGTG
n.) o AGTTGAAATCTGGAACTGCCT GTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTG
oe CTGTTGTGTGCCTGCTGAATA GTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAG
'a ACTTCTATCCCAGAGAGGCCA CCGTGCGAGGAGCAGTACGGCAGCACGTACCGTTGCGTCAG
oe cA
oe AAGTACAGTGGAAGGTGGAT CGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGG
AACGCCCTCCAATCGGGTAAC AGTACAAGTGCAAGGTGTCCAACAAAGCCCTCCCAGCCCCC
TCCCAGGAGAGTGTCACAGA ATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAG

n.) GCAGGACAGCAAGGACAGCA AACCACAGGTGTACACCCTGCCCCCATCCCGGGAGGAGATG
o CCTACAGCCTCAGCAGCACCC ACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTT
oe i-J
TGACGCTGAGCAAAGCAGAC CTATCCCAGCGATATCGCCGTGGAGTGGGAGAGCAATGGGC
c,.) --.1 TACGAGAAACACAAAGTCTA AGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGAC
o o CGCCTGCGAAGTCACCCATCA TCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGAC
--.1 GGGCCTGAGCTCGCCCGTCAC AAGAGTAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGT
AAAGAGCTTCAACAGGGGAG GATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCC
AGTGT TCTCCCTGTCTCCGGGTAAA
(SEQ ID NO: 1371 (SEQ ID NO: 1372 EIVLTQ SPATLSL SP GERATL SC QVQLVE SGGGVVQPGRSLRL SCAASGFTFSNYGMHWVRQAP
RASQSVDLHLAWYQQKPGQAP GEGLEWVAAIWFDASDKYYADAVKGRFTISRDNSKNTLYLQ
RLLIYEAATRATGIPDRFSGSGS MNSLRAEDTAVYYCARDLAIFGVVPDYWGQGTLVTVSSASTK
GTEFTLTISRLEPEDFAVYYCQ GP SVFPL AP S SKST S GGTAALGCLVKDYFPEPVTVSWN S GAL T
p QYQNWPLTFGGGTKVEIKRTV SGVHTFPAVLQS SGLY SLS SVVTVP S S SLGTQTYICNVNHKP SN

L.
AA AAPSVFIFPPSDEQLKSGTASVV TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLY
.
, CLLNNFYPREAKVQWKVDNAL ITREPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEE
..
QSGNSQESVTEQD SKD STY SL S QYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTIS
, STLTLSKADYEKHKVYACEVT KAKGQPREPQVYTLPP SREEMTKNQVSLTCLVKGFYPSDIAVE
.
, , HQGL S SPVTKSFNRGEC WE SNGQPENNYKTTPPVLD SD GSFFLY
SKL TVDKSRWQQGNV .
, L.
FSCSVMHEALHNHYTQKSLSLSPGK
, (SEQ ID NO: 1339) (SEQ ID NO: 1340) ATGGACATGAGGGTGCCCGCT ATGGACATGAGGGTGCCCGCTCAGCTCCTGGGGCTCCTGCT
CAGCTCCTGGGGCTCCTGCTG GCTGTGGCTGAGAGGTGCGCGCTGTCAGGTGCAGCTGGTGG
CTGTGGCTGAGAGGTGCGCGC AGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGA
TGTGAAATCGTGCTGACGCAG CTCTCCTGTGCAGCATCTGGATTCACCTTCAGTAACTATGGC
.7r o TCTCCAGCCACCCTGTCTCTG ATGCACTGGGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTG
.7r o TCTCCAGGGGAAAGAGCCAC

NA
n in CCTCTCCTGCAGGGCCAGTCA

ci3 0.0 GAGTGTTAACCTGAACTTAGC
TCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGC
¨
cp CTGGTACCAGCAGAAACCTG CGAGGACACGGCTGTGTATTACTGTGCGAGAGATTTGGCGA
n.) o GCCAGGCTCCCAGGCTCCTCA TTTTTGGAGTGGTCCCCGACTACTGGGGCCAGGGAACCCTG
oe TCTACCAGGCAGCCACCAGG GTCACCGTGTCTAGTGCCTCCACCAAGGGCCCATCGGTCTTC
'a GCCACTGGTATCCCAGACAGG CCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGC
oe cA
oe TTCAGTGGCAGTGGGTCTGGG GGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGG
ACAGAGTTCACTCTCACCATC TGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTG
AGCAGGCTGGAGCCTGAAGA CACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCC

n.) TTTTGCAGTTTATTACTGTCAG CTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCAC
=
CAGTATAACCAGTGGCCTCTC CCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACA
oe i-J
ACTTTCGGCGGAGGGACCAA CCAAGGTGGACAAGAAAGTTGAGCCCAAATCTTGTGACAAA
c,.) --.1 GGTGGAGATCAAACGAACGG ACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGG
o o TGGCTGCACCATCTGTCTTCA GGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACA
--.1 TCTTCCCGCCATCTGATGAGC CCCTCTACATCACCCGGGAGCCTGAGGTCACATGCGTGGTG
AGTTGAAATCTGGAACTGCCT GTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTG
CTGTTGTGTGCCTGCTGAATA GTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAG
ACTTCTATCCCAGAGAGGCCA CCGTGCGAGGAGCAGTACGGCAGCACGTACCGTTGCGTCAG
AAGTACAGTGGAAGGTGGAT CGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGG
AACGCCCTCCAATCGGGTAAC AGTACAAGTGCAAGGTGTCCAACAAAGCCCTCCCAGCCCCC
TCCCAGGAGAGTGTCACAGA ATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAG
GCAGGACAGCAAGGACAGCA AACCACAGGTGTACACCCTGCCCCCATCCCGGGAGGAGATG
P
CCTACAGCCTCAGCAGCACCC ACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTT
o L.
TGACGCTGAGCAAAGCAGAC CTATCCCAGCGATATCGCCGTGGAGTGGGAGAGCAATGGGC
.
, TACGAGAAACACAAAGTCTA AGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGAC
' CGCCTGCGAAGTCACCCATCA TCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGAC
" GGGCCTGAGCTCGCCCGTCAC
AAGAGTAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGT Lo':
, AAAGAGCTTCAACAGGGGAG GATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCC
.
, L.
AGTGT TCTCCCTGTCTCCGGGTAAA
, (SEQ ID NO: 1373 (SEQ ID NO: 1374 EIVLTQSPATLSLSPGERATLSC QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMHWVRQAP
RASQSVNLNLAWYQQKPGQAP GEGLEWVAAIWFDASDKYYADAVKGRFTISRDNSKNTLYLQ
RLLIYQAATRATGIPDRFSGSGS MNSLRAEDTAVYYCARDLAIFGVVPDYWGQGTLVTVSSASTK
GTEFTLTISRLEPEDFAVYYCQ GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALT
QYNQWPLTFGGGTKVEIKRTV SGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN
AA AAPSVFIFPPSDEQLKSGTASVV TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLY

n CLLNNFYPREAKVQWKVDNAL ITREPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEE

QSGNSQESVTEQDSKDSTYSLS QYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTIS
cp STLTLSKADYEKHKVYACEVT KAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVE
n.) o HQGLSSPVTKSFNRGEC
WESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNV
oe FSCSVMHEALHNHYTQKSLSLSPGK
'a (SEQ ID NO: 1349) (SEQ ID NO: 1350) oe cA
oe ATGGACATGAGGGTGCCCGCT ATGGACATGAGGGTGCCCGCTCAGCTCCTGGGGCTCCTGCT
CAGCTCCTGGGGCTCCTGCTG GCTGTGGCTGAGAGGTGCGCGCTGTCAGGTGCAGCTGGTGG
CTGTGGCTGAGAGGTGCGCGC AGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGA

t..) TGTGAAATCGTGCTGACGCAG CTCTCCTGTGCAGCATCTGGATTCACCTTCCAGAACTATGGC
o TCTCCAGCCACCCTGTCTCTG ATGCACTGGGTCCGCCAGGCTCCAGGCGAGGGGCTGGAGTG
oe TCTCCAGGGGAAAGAGCCAC GGTGGCAGCTATCTGGTTTGATGCGTCTGACAAATACTATG
c,.) --.1 CCTCTCCTGCAGGGCCAGTCA CAGACGCCGTGAAGGGCCGATTCACCATCTCCAGAGACAAC
o GAGTGTTTTCAGCCACTTAGC TCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGC
--.1 CTGGTACCAGCAGAAACCTG CGAGGACACGGCTGTGTATTACTGTGCGAGAGATCTTGCGA
GCCAGGCTCCCAGGCTCCTCA TTTTTGGAGTGGTCCCCGACTACTGGGGCCAGGGAACCCTG
TCTACGAAGCAGCCACCAGG GTCACCGTGTCTAGTGCCTCCACCAAGGGCCCATCGGTCTTC
GCCACTGGTATCCCAGACAGG CCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGC
TTCAGTGGCAGTGGGTCTGGG GGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGG
ACAGAGTTCACTCTCACCATC TGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTG
AGCAGGCTGGAGCCTGAAGA CACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCC
TTTTGCAGTTTATTACTGTCAG CTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCAC
P
in o CAGTATCAGAACTGGCCTCTC
CCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACA o 7r L.
NA ACTTTCGGCGGAGGGACCAA CCAAGGTGGACAAGAAAGTTGAGCCCAAATCTTGTGACAAA
.
, in GGTGGAGATCAAACGAACGG
ACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGG ' ci3 .
0.0 TGGCTGCACCATCTGTCTTCA
GGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACA " --TCTTCCCGCCATCTGATGAGC CCCTCTACATCACCCGGGAGCCTGAGGTCACATGCGTGGTG
y , AGTTGAAATCTGGAACTGCCT GTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTG
.
, L.
CTGTTGTGTGCCTGCTGAATA GTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAG
, ACTTCTATCCCAGAGAGGCCA CCGTGCGAGGAGCAGTACGGCAGCACGTACCGTTGCGTCAG
AAGTACAGTGGAAGGTGGAT CGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGG
AACGCCCTCCAATCGGGTAAC AGTACAAGTGCAAGGTGTCCAACAAAGCCCTCCCAGCCCCC
TCCCAGGAGAGTGTCACAGA ATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAG
GCAGGACAGCAAGGACAGCA AACCACAGGTGTACACCCTGCCCCCATCCCGGGAGGAGATG
CCTACAGCCTCAGCAGCACCC ACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTT
TGACGCTGAGCAAAGCAGAC CTATCCCAGCGATATCGCCGTGGAGTGGGAGAGCAATGGGC

TACGAGAAACACAAAGTCTA AGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGAC
n ,-i CGCCTGCGAAGTCACCCATCA TCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGAC
GGGCCTGAGCTCGCCCGTCAC AAGAGTAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGT
cp n.) o AAAGAGCTTCAACAGGGGAG GATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCC
oe AGTGT TCTCCCTGTCTCCGGGTAAA
(SEQ ID NO: 1375 (SEQ ID NO: 1376 oe cA
oe EIVLTQ SPATLSL SP GERATL SC QVQLVE SGGGVVQPGRSLRL SCAASGFTFQNYGMHWVRQAP
RASQSVFSHLAWYQQKPGQAP GEGLEWVAAIWFDASDKYYADAVKGRFTISRDNSKNTLYLQ
RLLIYEAATRATGIPDRFSGSGS MNSLRAEDTAVYYCARDLAIFGVVPDYWGQGTLVTVSSASTK

n.) GTEFTLTISRLEPEDFAVYYCQ GP SVFPL AP S SKST S GGTAALGCLVKDYFPEPVTVSWN S GAL T
=
QYQNWPLTFGGGTKVEIKRTV SGVHTFPAVLQS SGLY SLS SVVTVP S S SLGTQTYICNVNHKP SN
oe i-J
AA AAPSVFIFPPSDEQLKSGTASVV TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLY
c,.) --.1 CLLNNFYPREAKVQWKVDNAL ITREPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEE
o o QSGNSQESVTEQD SKD STY SL S QYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTIS
--.1 STLTLSKADYEKHKVYACEVT KAKGQPREPQVYTLPP SREEMTKNQVSLTCLVKGFYPSDIAVE
HQGL S SPVTKSFNRGEC WE SNGQPENNYKTTPPVLD SD GSFFLY
SKL TVDKSRWQQGNV
FSCSVMHEALHNHYTQKSLSLSPGK
(SEQ ID NO: 1359) (SEQ ID NO: 1360) P
.
L.
.
,, , L.
,, .
, L.
, , .
, L.
, n ,-i cp t.., =
oe 'a oe cA
oe [0203] In one embodiment the antibody or fragment thereof comprises a light chain variable region comprising a sequence selected from the group consisting of SEQ ID NOs:
723, 727, 731, 735, 739, 743, 747, 751, 755, 759, 763, 767, 771, 775, 779, 783, 787, 791, 795, 799, 803, 807, 811, 815, 819, 823, 827, 831, 835, 839, 843, 847, 851, 855, 859, 863, 867, 871, 875, 879, 883, 887, 891, 895, 899, 903, 907, 911, 915, 919, 923, 927, 931, 935, 939, 943, 947, 951, 955, 959, 1286, 1296, 1306, 1316, 1326, 1336, 1346, and 1356. In one embodiment the antibody or fragment thereof comprises a heavy chain variable region comprising a sequence selected from the group consisting of SEQ ID NOs: 724, 728, 732, 736, 740, 744, 748, 752, 756, 760, 764, 768, 772, 776, 780, 784, 788, 792, 796, 800, 804, 808, 812, 816, 820, 824, 828, 832, 836, 840, 844, 848, 852, 856, 860, 864, 868, 872, 876, 880, 884, 888, 892, 896, 900, 904, 908, 912, 916, 920, 924, 928, 932, 936, 940, 944, 948, 952, 956, 960, 1287, 1297, 1307, 1317, 1327, 1337, 1347, and 1357. In one embodiment the antibody or fragment thereof comprises a light chain variable region comprising a sequence selected from the group consisting of SEQ ID NOs: 723, 727, 731, 735, 739, 743, 747, 751, 755, 759, 763, 767,771,775,779,783,787,791,795,799,803,807,811,815,819,823,827,831,835, 839,843,847,851,855,859,863,867,871,875,879,883,887,891,895,899,903,907, 911,915,919,923,927,931,935,939,943,947,951,955,959,1286,1296,1306,1316, 1326, 1336, 1346, and 1356 and a heavy chain variable region comprising a sequence selected from the group consisting of SEQ ID NOs: 724, 728, 732, 736, 740, 744, 748, 752, 756, 760, 764, 768, 772, 776, 780, 784, 788, 792, 796, 800, 804, 808, 812, 816, 820, 824, 828, 832, 836, 840, 844, 848, 852, 856, 860, 864, 868, 872, 876, 880, 884, 888, 892, 896, 900, 904, 908, 912, 916, 920, 924, 928, 932, 936, 940, 944, 948, 952, 956, 960, 1287, 1297, 1307, 1317, 1327, 1337, 1347, and 1357.
[0204] In one embodiment the antibody or fragment thereof comprises a combination of light chain variable region and a heavy chain variable region selected from the group consisting of a light chain variable region comprising SEQ ID NO: 723 and a heavy chain variable region comprising SEQ ID NO: 724; a light chain variable region comprising SEQ ID NO:
727 and a heavy chain variable region comprising SEQ ID NO: 728; a light chain variable region comprising SEQ ID NO: 731 and a heavy chain variable region comprising SEQ ID
NO: 732;
a light chain variable region comprising SEQ ID NO: 735 and a heavy chain variable region comprising SEQ ID NO: 736; a light chain variable region comprising SEQ ID NO:
739 and a heavy chain variable region comprising SEQ ID NO: 740; a light chain variable region comprising SEQ ID NO: 743 and a heavy chain variable region comprising SEQ ID
NO: 744;
a light chain variable region comprising SEQ ID NO: 747 and a heavy chain variable region comprising SEQ ID NO: 748; a light chain variable region comprising SEQ ID NO:
751 and a heavy chain variable region comprising SEQ ID NO: 752; a light chain variable region comprising SEQ ID NO: 755 and a heavy chain variable region comprising SEQ ID
NO: 756;
a light chain variable region comprising SEQ ID NO: 759 and a heavy chain variable region comprising SEQ ID NO: 760; a light chain variable region comprising SEQ ID NO:
763 and a heavy chain variable region comprising SEQ ID NO: 764; a light chain variable region comprising SEQ ID NO: 767 and a heavy chain variable region comprising SEQ ID
NO: 768;
a light chain variable region comprising SEQ ID NO: 771 and a heavy chain variable region comprising SEQ ID NO: 772; a light chain variable region comprising SEQ ID NO:
775 and a heavy chain variable region comprising SEQ ID NO: 776; a light chain variable region comprising SEQ ID NO: 779 and a heavy chain variable region comprising SEQ ID
NO: 780;
a light chain variable region comprising SEQ ID NO: 783 and a heavy chain variable region comprising SEQ ID NO: 784; a light chain variable region comprising SEQ ID NO:
787 and a heavy chain variable region comprising SEQ ID NO: 788; a light chain variable region comprising SEQ ID NO: 791 and a heavy chain variable region comprising SEQ ID
NO: 792;
a light chain variable region comprising SEQ ID NO: 795 and a heavy chain variable region comprising SEQ ID NO: 796; a light chain variable region comprising SEQ ID NO:
799 and a heavy chain variable region comprising SEQ ID NO: 800; a light chain variable region comprising SEQ ID NO: 803 and a heavy chain variable region comprising SEQ ID
NO: 804;
a light chain variable region comprising SEQ ID NO: 807 and a heavy chain variable region comprising SEQ ID NO: 808; a light chain variable region comprising SEQ ID NO:
811 and a heavy chain variable region comprising SEQ ID NO: 812; a light chain variable region comprising SEQ ID NO: 815 and a heavy chain variable region comprising SEQ ID
NO: 816;
a light chain variable region comprising SEQ ID NO: 819 and a heavy chain variable region comprising SEQ ID NO: 820; a light chain variable region comprising SEQ ID NO:
823 and a heavy chain variable region comprising SEQ ID NO: 824; a light chain variable region comprising SEQ ID NO: 827 and a heavy chain variable region comprising SEQ ID
NO: 828;
a light chain variable region comprising SEQ ID NO: 831 and a heavy chain variable region comprising SEQ ID NO: 832; a light chain variable region comprising SEQ ID NO:
835 and a heavy chain variable region comprising SEQ ID NO: 836; a light chain variable region comprising SEQ ID NO: 839 and a heavy chain variable region comprising SEQ ID
NO: 840;
a light chain variable region comprising SEQ ID NO: 843 and a heavy chain variable region comprising SEQ ID NO: 844; a light chain variable region comprising SEQ ID NO:
847 and a heavy chain variable region comprising SEQ ID NO: 848; a light chain variable region comprising SEQ ID NO: 851 and a heavy chain variable region comprising SEQ ID
NO: 852;
a light chain variable region comprising SEQ ID NO: 855 and a heavy chain variable region comprising SEQ ID NO: 856; a light chain variable region comprising SEQ ID NO:
859 and a heavy chain variable region comprising SEQ ID NO: 860; a light chain variable region comprising SEQ ID NO: 863 and a heavy chain variable region comprising SEQ ID
NO: 864;
a light chain variable region comprising SEQ ID NO: 867 and a heavy chain variable region comprising SEQ ID NO: 868; a light chain variable region comprising SEQ ID NO:
871 and a heavy chain variable region comprising SEQ ID NO: 872; a light chain variable region comprising SEQ ID NO: 875 and a heavy chain variable region comprising SEQ ID
NO: 876;
a light chain variable region comprising SEQ ID NO: 879 and a heavy chain variable region comprising SEQ ID NO: 880; a light chain variable region comprising SEQ ID NO:
883 and a heavy chain variable region comprising SEQ ID NO: 884; a light chain variable region comprising SEQ ID NO: 887 and a heavy chain variable region comprising SEQ ID
NO: 888;
a light chain variable region comprising SEQ ID NO: 891 and a heavy chain variable region comprising SEQ ID NO: 892; a light chain variable region comprising SEQ ID NO:
895 and a heavy chain variable region comprising SEQ ID NO: 896; a light chain variable region comprising SEQ ID NO: 899 and a heavy chain variable region comprising SEQ ID
NO: 900;
a light chain variable region comprising SEQ ID NO: 903 and a heavy chain variable region comprising SEQ ID NO: 904; a light chain variable region comprising SEQ ID NO:
907 and a heavy chain variable region comprising SEQ ID NO: 908; a light chain variable region comprising SEQ ID NO: 911 and a heavy chain variable region comprising SEQ ID
NO: 912;
a light chain variable region comprising SEQ ID NO: 915 and a heavy chain variable region comprising SEQ ID NO: 916; a light chain variable region comprising SEQ ID NO:
919 and a heavy chain variable region comprising SEQ ID NO: 920; a light chain variable region comprising SEQ ID NO: 923 and a heavy chain variable region comprising SEQ ID
NO: 924;
a light chain variable region comprising SEQ ID NO: 927 and a heavy chain variable region comprising SEQ ID NO: 928; a light chain variable region comprising SEQ ID NO:
931 and a heavy chain variable region comprising SEQ ID NO: 932; a light chain variable region comprising SEQ ID NO: 935 and a heavy chain variable region comprising SEQ ID
NO: 936;
a light chain variable region comprising SEQ ID NO: 939 and a heavy chain variable region comprising SEQ ID NO: 940; a light chain variable region comprising SEQ ID NO:
943 and a heavy chain variable region comprising SEQ ID NO: 944; a light chain variable region comprising SEQ ID NO: 947 and a heavy chain variable region comprising SEQ ID
NO: 948;
a light chain variable region comprising SEQ ID NO: 951 and a heavy chain variable region comprising SEQ ID NO: 952; a light chain variable region comprising SEQ ID NO:
955 and a heavy chain variable region comprising SEQ ID NO: 956; a light chain variable region comprising SEQ ID NO: 959 and a heavy chain variable region comprising SEQ ID
NO: 960;
a light chain variable region comprising SEQ ID NO: 1286 and a heavy chain variable region comprising SEQ ID NO: 1287; a light chain variable region comprising SEQ ID
NO: 1296 and a heavy chain variable region comprising SEQ ID NO: 1297; a light chain variable region comprising SEQ ID NO: 1306 and a heavy chain variable region comprising SEQ ID
NO: 1307; a light chain variable region comprising SEQ ID NO: 1316 and a heavy chain variable region comprising SEQ ID NO: 1317; alight chain variable region comprising SEQ
ID NO: 1326 and a heavy chain variable region comprising SEQ ID NO: 1327; a light chain variable region comprising SEQ ID NO: 1336 and a heavy chain variable region comprising SEQ ID NO: 1337; alight chain variable region comprising SEQ ID NO: 1346 and a heavy chain variable region comprising SEQ ID NO: 1347; and a light chain variable region comprising SEQ ID NO: 1356 and a heavy chain variable region comprising SEQ ID
NO:
1357.
[0205] In one embodiment the antibody or fragment thereof comprises a light chain variable region encoded by a polynucleotide sequence selected from the group consisting of SEQ ID
1`0Ds:721,725,729,733,737,741,745,749,753,757,761,765,769,773,777,781,785, 789,793,797,801,805,809,813,817,821,825,829,833,837,841,845,849,853,857, 861,865,869,873,877,881,885,889,893,897,901,905,909,913,917,921,925,929, 933,937,941,945,949,953,955,1377,1379,1381,1383,1385,1387,1389, mul1391.In one embodiment the antibody or fragment thereof comprises a heavy chain variable region encoded by a polynucleotide selected from the group consisting of SEQ ID NOs:
722, 726, 730, 734, 738, 742, 746, 750, 754, 758, 762, 766, 770, 774, 778, 782, 786, 790, 794, 798, 802, 806, 810, 814, 818, 822, 826, 830, 834, 838, 842, 846, 850, 854, 858, 862, 866, 870, 874, 878, 882, 886, 890, 894, 898, 902, 906, 910, 914, 918, 922, 926, 930, 934, 938, 942, 946, 950, 954, 958, 1378, 1380, 1382, 1384, 1386, 1388, 1390, and 1392. In one embodiment the antibody or fragment thereof comprises a light chain variable region encoded by a polynucleotide sequence selected from the group consisting of SEQ ID NOs: 721, 725, 729, 733, 737, 741, 745, 749, 753, 757, 761, 765, 769, 773, 777, 781, 785, 789, 793, 797, 801, 805, 809, 813, 817, 821, 825, 829, 833, 837, 841, 845, 849, 853, 857, 861, 865, 869, 873, 877, 881, 885, 889, 893, 897, 901, 905, 909, 913, 917, 921, 925, 929, 933, 937, 941, 945, 949, 953, 955, 1377, 1379, 1381, 1383, 1385, 1387, 1389, and 1391 and a heavy chain variable region encoded by a polynucleotide sequence selected from the group consisting of SEQ ID NOs: 722, 726, 730, 734, 738, 742, 746, 750, 754, 758, 762, 766, 770, 774, 778, 782, 786, 790, 794, 798, 802, 806, 810, 814, 818, 822, 826, 830, 834, 838, 842, 846, 850, 854, 858, 862, 866, 870, 874, 878, 882, 886, 890, 894, 898, 902, 906, 910, 914, 918, 922, 926, 930, 934, 938, 942, 946, 950, 954, 958, 1378, 1380, 1382, 1384, 1386, 1388, 1390, and 1392.
In one embodiment the antibody or fragment thereof comprises a combination of light chain variable region and a heavy chain variable region selected from the group consisting of a light chain variable region encoded by a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 721 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 722; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 725 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO:
726; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID
NO: 729 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID
NO: 730; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 733 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 734; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 737 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 738; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 741 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 742; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 745 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO:
746; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID
NO: 749 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID
NO: 750; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 753 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 754; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 757 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 758; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 761 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 762; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 765 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO:
766; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID
NO: 769 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID
NO: 770; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 773 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 774; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 777 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 778; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 781 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 782; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 785 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO:
786; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID
NO: 789 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID
NO: 790; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 793 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 794; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 797 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 798; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 801 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 802; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 805 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO:
806; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID
NO: 809 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID
NO: 810; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 813 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 814; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 817 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 818; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 821 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 822; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 825 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO:
826; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID
NO: 829 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID

NO: 830; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 833 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 834; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 837 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 838; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 841 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 842; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 845 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO:
846; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID
NO: 849 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID
NO: 850; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 853 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 854; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 857 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 858; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 861 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 862; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 865 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO:
866; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID
NO: 869 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID
NO: 870; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 873 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 874; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 877 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 878; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 881 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 882; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 885 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO:
886; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID
NO: 889 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID
NO: 890; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 893 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 894; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 897 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 898; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 901 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 902; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 905 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO:
906; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID
NO: 909 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID
NO: 910; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 913 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 914; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 917 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 918; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 921 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 922; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 925 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO:
926; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID
NO: 929 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID
NO: 930; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 933 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 934; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 937 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 938; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 941 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 942; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 945 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO:
946; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID
NO: 949 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID
NO: 950; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 953 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 954; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 957 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 958; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 1377 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 1378; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO:
1379 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO:
1380; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID
NO: 1381 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 1382; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 1383 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 1384; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 1385 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 1386; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO:
1387 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO:
1388; a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID
NO: 1389 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 1390; and a light chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 1391 and a heavy chain variable region encoded by a polynucleotide sequence comprising SEQ ID NO: 1392.
[0206] Some antigen binding proteins comprise a variable light domain and a variable heavy domain as listed in one of the rows for one of the antibodies listed in TABLE
3. In some instances, the antigen binding protein comprises two identical variable light domains and two identical variable heavy domains from one of the antibodies listed in TABLE 3.
Some antigen binding proteins that are provided comprise a variable light domain and a variable heavy domain as listed in one of the rows for one of the antibodies listed in TABLE 3, except that one or both of the domains differs from the sequence specified in the table at only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 amino acid residues, wherein each such sequence difference is independently either a single amino acid deletion, insertion or substitution, with the deletions, insertions and/or substitutions resulting in no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 amino acid changes relative to the variable domain sequences specified in TABLE 3. In one embodiment, the antigen binding protein comprises a variable region sequence from Table 3, but with the N-terminal methionine deleted.
Other antigen binding proteins also comprise a variable light domain and a variable heavy domain as listed in one of the rows for one of the antibodies listed in TABLE 3, except that one or both of the domains differs from the sequence specified in the table in that the heavy chain variable domain and/or light chain variable domain comprises or consists of a sequence of amino acids that has at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%
sequence identity to the amino acid sequences of the heavy chain variable domain or light chain variable domain sequences as specified in TABLE 3.
[0207] In another aspect, the antigen binding protein consists just of a variable light or variable heavy domain from an antibody listed in TABLE 3. In still another aspect, the antigen binding protein comprises two or more of the same variable heavy domains or two or more of the same variable light domains from those listed in TABLE 3. Such domain antibodies can be fused together or joined via a linker as described in greater detail below.
The domain antibodies can also be fused or linked to one or more molecules to extend the half-life (e.g., PEG or albumin).
[0208] In certain embodiments it is desired that the antigen binding protein is an antibody with reduced viscosity. Such of antigen binding proteins can be produced by modifying sequences in framework regions and/or the Fc domain that are shown to be associated with high viscosity.
[0209] Such reduced-viscosity antigen binding proteins included antibodies wherein:
[0210] the VH111-18 germline subfamily sequence comprises one or more substitutions selected from 82R, 94S, and 95R;
[0211] the VH313-33 germline subfamily sequence comprises one or more of substitutions 1E, 17G, and 85A;
[0212] the VK31L16 germline subfamily sequence comprises one or more substitutions selected from 4L, 13L, 76D, 95R, 97E, and 98P;
[0213] the VK31L6 germline subfamily sequence comprises one or more substitutions selected from 76D and 95R;
[0214] the Fc domain sequence comprises one or more substitutions selected from 253A, 440K, and 439E; and [0215] the Fc domain C-terminus comprises a sequence selected from KP, KKP, KKKP, and E..
[0216] All of the foregoing preferred viscosity-reducing amino acid substitutions in variable regions are identified by the Aho numbering system. All viscosity-reducing residues in conserved regions including Fc are identified by the EU numbering system.

[0217]
[0218] Other antigen binding proteins that are provided are variants of antibodies formed by combination of the heavy and light chains shown in TABLE 3 and comprise light and/or heavy chains that each have at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequences of these chains. In some instances, such antibodies include at least one heavy chain and one light chain, whereas in other instances the variant forms contain two identical light chains and two identical heavy chains.
[0219] The various combinations of heavy chain variable regions may be combined with any of the various combinations of light chain variable regions.
[0220] In a further embodiment, the isolated antigen binding protein provided herein is a human antibody comprising a sequence as set forth in TABLE 3 and is of the IgGi-, IgG2-IgG3- or IgG4-type.
[0221] The antigen binding proteins disclosed herein are polypeptides into which one or more CDRs are grafted, inserted and/or joined. An antigen binding protein can have 1, 2, 3, 4, or 6 CDRs. An antigen binding protein thus can have, for example, one heavy chain CDR1 ("CDRH1"), and/or one heavy chain CDR2 ("CDRH2"), and/or one heavy chain CDR3 ("CDRH3"), and/or one light chain CDR1 ("CDRL1"), and/or one light chain CDR2 ("CDRL2"), and/or one light chain CDR3 ("CDRL3"). Some antigen binding proteins include both a CDRH3 and a CDRL3. Specific light and heavy chain CDRs are identified in TABLEs 4A and 4B, respectively.
[0222] Complementarity determining regions (CDRs) and framework regions (FR) of a given antibody may be identified using the system described by Kabat et al. in Sequences of Proteins of Immunological Interest, 5th Ed., US Dept. of Health and Human Services, PHS, NIH, NIH Publication no. 91-3242, 1991. Certain antibodies that are disclosed herein comprise one or more amino acid sequences that are identical or have substantial sequence identity to the amino acid sequences of one or more of the CDRs presented in and 4B. These CDRs use the system described by Kabat et al. as noted above.
[0223] The structure and properties of CDRs within a naturally occurring antibody has been described, supra. Briefly, in a traditional antibody, the CDRs are embedded within a framework in the heavy and light chain variable region where they constitute the regions responsible for antigen binding and recognition. A variable region comprises at least three heavy or light chain CDRs, see, supra (Kabat etal., 1991, Sequences of Proteins of Immunological Interest, Public Health Service N.I.H., Bethesda, MD; see also Chothia and Lesk, 1987,1 Mol. Biol. 196:901-917; Chothia etal., 1989, Nature 342: 877-883), within a framework region (designated framework regions 1-4, FR1, FR2, FR3, and FR4, by Kabat et al., 1991, supra; see also Chothia and Lesk, 1987, supra). The CDRs provided herein, however, may not only be used to define the antigen binding domain of a traditional antibody structure, but may be embedded in a variety of other polypeptide structures, as described herein.
[0224] In one embodiment the antibody or fragment thereof comprises a CDRL1, a CDRL2, a CDRL3, a CDRH1, a CDRH2, and a CDRH3. In one embodiment the antibody or fragment thereof comprises a CDRL1 comprising a sequence selected from the group consisting of SEQ ID NOs: 4, 10, 16, 22, 28, 34, 40, 46, 52, 58, 64, 70, 76, 82, 88, 94, 100, 106, 112, 118, 124, 130, 136, 142, 148, 154, 160, 166, 172, 178, 184, 190, 196, 202, 208, 214, 220, 226, 232, 238, 244, 250, 256, 262, 268, 274, 280, 286, 292, 298, 304, 310, 316, 322, 328, 334, 340, 346, 352, 358, 1290, 1300, 1310, 1320, 1330, 1340, and 1350. In one embodiment the antibody or fragment thereof comprises a CDRL2 comprising a sequence selected from the group consisting of SEQ ID NOs: 5, 11, 17, 23, 29, 35, 41, 47, 53, 59, 65, 71, 77, 83, 89, 95, 101, 107, 113, 119, 125, 131, 137, 143, 149, 155, 161, 167, 173, 179, 185, 191, 197, 203, 209, 215, 221, 227, 233, 239, 245, 251, 257, 263, 269, 275, 281, 287, 293, 299, 305, 311, 317, 323, 329, 335, 341, 347, 353, 359, 1291, 1301, 1311, 1321, 1331, 1341, and 1351. In one embodiment the antibody or fragment thereof comprises a CDRL3 comprising a sequence selected from the group consisting of SEQ ID NOs: 6, 12, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, 102, 108, 114, 120, 126, 132, 138, 144, 150, 156, 162, 168, 174, 180, 186, 192, 198, 204, 210, 216, 222, 228, 234, 240, 246, 252, 258, 264, 270, 276, 282, 288, 294, 300, 306, 312, 318, 324, 330, 336, 342, 348, 354, 360, 1292, 1302, 1312, 1322, 1332, 1342, and 1352. In one embodiment the antibody or fragment thereof comprises a CDRH1 comprising a sequence selected from the group consisting of SEQ ID NOs:
364, 370, 376, 382, 388, 394, 400, 406, 412, 418, 424, 430, 436, 442, 448, 454, 460, 466, 472, 478, 484, 490, 496, 502, 508, 514, 520, 526, 532, 538, 544, 550, 556, 562, 568, 574, 580, 586, 592, 598, 604, 610, 616, 622, 628, 634, 640, 646, 652, 658, 664, 670, 676, 682, 688, 694, 700, 706, 712, 718, 1293, 1303, 1313, 1323, 1333, 1343, and 1353. In one embodiment the antibody or fragment thereof comprises a CDRH2 comprising a sequence selected from the group consisting of SEQ ID NOs: 365, 371, 377, 383, 389, 395, 401, 407, 413, 419, 425, 431, 437, 443, 449, 455, 461, 467, 473, 479, 485, 491, 497, 503, 509, 515, 521, 527, 533, 539, 545, 551, 557, 563, 569, 575, 581, 587, 593, 599, 605, 611, 617, 623, 629, 635, 641, 647, 653, 659, 665, 671, 677, 683, 689, 695, 701, 707, 713, 719, 1294, 1304, 1314, 1324, 1334, 1344, and 1354. In one embodiment the antibody or fragment thereof comprises a comprising a sequence selected from the group consisting of SEQ ID NOs: 366, 372, 378, 384, 390, 396, 402, 408, 414, 420, 426, 432, 438, 444, 450, 456, 462, 468, 474, 480, 486, 492, 498, 504, 510, 516, 522, 528, 534, 540, 546, 552, 558, 564, 570, 576, 582, 588, 594, 600, 606, 612, 618, 624, 630, 636, 642, 648, 654, 660, 666, 672, 678, 684, 690, 696, 702, 708, 714, 720, 1295, 1305, 1315, 1325, 1335, 1345, and 1355. In one embodiment the antibody or fragment thereof comprises a CDRL1, a CDRL2, a CDRL3, a CDRH1, a CDRH2, and a CDRH3, wherein each CDRL1, CDRL2, CDRL3, CDRH1, CDRH2, and CDRH3, respectively, comprises a sequence selected from the group consisting of SEQ ID
NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 364, SEQ ID NO: 365, and SEQ ID
NO:
366; SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 370, SEQ ID NO:
371, and SEQ ID NO: 372; SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO:
376, SEQ ID NO: 377, and SEQ ID NO: 378; SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO:
24, SEQ ID NO: 382, SEQ ID NO: 383, and SEQ ID NO: 384; SEQ ID NO: 28, SEQ ID NO:
29, SEQ ID NO: 30, SEQ ID NO: 388, SEQ ID NO: 389, and SEQ ID NO: 390; SEQ ID NO:
34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 394, SEQ ID NO: 395, and SEQ ID NO:
396;
SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 400, SEQ ID NO: 401, and SEQ ID NO: 402; SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 406, SEQ
ID NO: 407, and SEQ ID NO: 408; SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ
ID NO: 412, SEQ ID NO: 413, and SEQ ID NO: 414; SEQ ID NO: 58, SEQ ID NO: 59, SEQ
ID NO: 60, SEQ ID NO: 418, SEQ ID NO: 419, and SEQ ID NO: 420; SEQ ID NO: 64, SEQ
ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 424, SEQ ID NO: 425, and SEQ ID NO: 426;
SEQ
ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 430, SEQ ID NO: 431, and SEQ
ID NO: 432; SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 436, SEQ
ID
NO: 437, and SEQ ID NO: 438; SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ
ID
NO: 442, SEQ ID NO: 443, and SEQ ID NO: 444; SEQ ID NO: 88, SEQ ID NO: 89, SEQ
ID
NO: 90, SEQ ID NO: 448, SEQ ID NO: 449, and SEQ ID NO: 450; SEQ ID NO: 94, SEQ
ID
NO: 95, SEQ ID NO: 96, SEQ ID NO: 454, SEQ ID NO: 455, and SEQ ID NO: 456; SEQ
ID
NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 460, SEQ ID NO: 461, and SEQ
ID NO: 462; SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 466, SEQ
ID NO: 467, and SEQ ID NO: 468; SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO:
114, SEQ ID NO: 472, SEQ ID NO: 473, and SEQ ID NO: 474; SEQ ID NO: 118, SEQ ID NO:

119, SEQ ID NO: 120, SEQ ID NO: 478, SEQ ID NO: 479, and SEQ ID NO: 480; SEQ
ID
NO: 124, SEQ ID NO: 125, SEQ ID NO: 126, SEQ ID NO: 484, SEQ ID NO: 485, and SEQ
ID NO: 486; SEQ ID NO: 130, SEQ ID NO: 131, SEQ ID NO: 132, SEQ ID NO: 490, SEQ

ID NO: 491, and SEQ ID NO: 492; SEQ ID NO: 136, SEQ ID NO: 137, SEQ ID NO:
138, SEQ ID NO: 496, SEQ ID NO: 497, and SEQ ID NO: 498; SEQ ID NO: 142, SEQ ID NO:

143, SEQ ID NO: 144, SEQ ID NO: 502, SEQ ID NO: 503, and SEQ ID NO: 504; SEQ
ID
NO: 148, SEQ ID NO: 149, SEQ ID NO: 150, SEQ ID NO: 508, SEQ ID NO: 509, and SEQ
ID NO: 510; SEQ ID NO: 154, SEQ ID NO: 155, SEQ ID NO: 156, SEQ ID NO: 514, SEQ
ID NO: 515, and SEQ ID NO: 516; SEQ ID NO: 160, SEQ ID NO: 161, SEQ ID NO:
162, SEQ ID NO: 520, SEQ ID NO: 521, and SEQ ID NO: 522; SEQ ID NO: 166, SEQ ID NO:

167, SEQ ID NO: 168, SEQ ID NO: 526, SEQ ID NO: 527, and SEQ ID NO: 528; SEQ
ID
NO: 172, SEQ ID NO: 173, SEQ ID NO: 174, SEQ ID NO: 532, SEQ ID NO: 533, and SEQ
ID NO: 534; SEQ ID NO: 178, SEQ ID NO: 179, SEQ ID NO: 180, SEQ ID NO: 538, SEQ
ID NO: 539, and SEQ ID NO: 540; SEQ ID NO: 184, SEQ ID NO: 185, SEQ ID NO:
186, SEQ ID NO: 544, SEQ ID NO: 545, and SEQ ID NO: 546; SEQ ID NO: 190, SEQ ID NO:

191, SEQ ID NO: 192, SEQ ID NO: 550, SEQ ID NO: 551, and SEQ ID NO: 552; SEQ
ID
NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 556, SEQ ID NO: 557, and SEQ
ID NO: 558; SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQ ID NO: 562, SEQ
ID NO: 563, and SEQ ID NO: 564; SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO:
210, SEQ ID NO: 568, SEQ ID NO: 569, and SEQ ID NO: 570; SEQ ID NO: 214, SEQ ID NO:

215, SEQ ID NO: 216, SEQ ID NO: 574, SEQ ID NO: 575, and SEQ ID NO: 576; SEQ
ID
NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 580, SEQ ID NO: 581, and SEQ
ID NO: 582; SEQ ID NO: 226, SEQ ID NO: 227, SEQ ID NO: 228, SEQ ID NO: 586, SEQ
ID NO: 587, and SEQ ID NO: 588; SEQ ID NO: 232, SEQ ID NO: 233, SEQ ID NO:
234, SEQ ID NO: 592, SEQ ID NO: 593, and SEQ ID NO: 594; SEQ ID NO: 238, SEQ ID NO:

239, SEQ ID NO: 240, SEQ ID NO: 598, SEQ ID NO: 599, and SEQ ID NO: 600; SEQ
ID
NO: 244, SEQ ID NO: 245, SEQ ID NO: 246, SEQ ID NO: 604, SEQ ID NO: 605, and SEQ
ID NO: 606; SEQ ID NO: 250, SEQ ID NO: 251, SEQ ID NO: 252, SEQ ID NO: 610, SEQ
ID NO: 611, and SEQ ID NO: 612; SEQ ID NO: 256, SEQ ID NO: 257, SEQ ID NO:
258, SEQ ID NO: 616, SEQ ID NO: 617, and SEQ ID NO: 618; SEQ ID NO: 262, SEQ ID NO:

263, SEQ ID NO: 264, SEQ ID NO: 622, SEQ ID NO: 623, and SEQ ID NO: 624; SEQ
ID
NO: 268, SEQ ID NO: 269, SEQ ID NO: 270, SEQ ID NO: 628, SEQ ID NO: 629, and SEQ
ID NO: 630; SEQ ID NO: 274, SEQ ID NO: 275, SEQ ID NO: 276, SEQ ID NO: 634, SEQ
ID NO: 635, and SEQ ID NO: 636; SEQ ID NO: 280, SEQ ID NO: 281, SEQ ID NO:
282, SEQ ID NO: 640, SEQ ID NO: 641, and SEQ ID NO: 642; SEQ ID NO: 286, SEQ ID NO:

287, SEQ ID NO: 288, SEQ ID NO: 646, SEQ ID NO: 647, and SEQ ID NO: 648; SEQ
ID
NO: 292, SEQ ID NO: 293, SEQ ID NO: 294, SEQ ID NO: 652, SEQ ID NO: 653, and SEQ

ID NO: 654; SEQ ID NO: 298, SEQ ID NO: 299, SEQ ID NO: 300, SEQ ID NO: 658, SEQ
ID NO: 659, and SEQ ID NO: 660; SEQ ID NO: 304, SEQ ID NO: 305, SEQ ID NO:
306, SEQ ID NO: 664, SEQ ID NO: 665, and SEQ ID NO: 666; SEQ ID NO: 310, SEQ ID NO:

311, SEQ ID NO: 312, SEQ ID NO: 670, SEQ ID NO: 671, and SEQ ID NO: 672; SEQ
ID
NO: 316, SEQ ID NO: 317, SEQ ID NO: 318, SEQ ID NO: 676, SEQ ID NO: 677, and SEQ
ID NO: 678; SEQ ID NO: 322, SEQ ID NO: 323, SEQ ID NO: 324, SEQ ID NO: 682, SEQ
ID NO: 683, and SEQ ID NO: 684; SEQ ID NO: 328, SEQ ID NO: 329, SEQ ID NO:
330, SEQ ID NO: 688, SEQ ID NO: 689, and SEQ ID NO: 690; SEQ ID NO: 334, SEQ ID NO:

335, SEQ ID NO: 336, SEQ ID NO: 694, SEQ ID NO: 695, and SEQ ID NO: 696; SEQ
ID
NO: 340, SEQ ID NO: 341, SEQ ID NO: 342, SEQ ID NO: 700, SEQ ID NO: 701, and SEQ
ID NO: 702; SEQ ID NO: 346, SEQ ID NO: 347, SEQ ID NO: 348, SEQ ID NO: 706, SEQ
ID NO: 707, and SEQ ID NO: 708; SEQ ID NO: 352, SEQ ID NO: 353, SEQ ID NO:
354, SEQ ID NO: 712, SEQ ID NO: 713, and SEQ ID NO: 714; SEQ ID NO: 358, SEQ ID NO:

359, SEQ ID NO: 360, SEQ ID NO: 718, SEQ ID NO: 719, and SEQ ID NO: 720; SEQ
ID
NO: 1290, SEQ ID NO: 1291, SEQ ID NO: 1292, SEQ ID NO: 1293, SEQ ID NO: 1294, and SEQ ID NO: 1295; SEQ ID NO: 1300, SEQ ID NO: 1301, SEQ ID NO: 1302, SEQ ID NO:

1303, SEQ ID NO: 1304, and SEQ ID NO: 1305; SEQ ID NO: 1310, SEQ ID NO: 1311, SEQ ID NO: 1312, SEQ ID NO: 1313, SEQ ID NO: 1314, and SEQ ID NO: 1315; SEQ ID

NO: 1320, SEQ ID NO: 1321, SEQ ID NO: 1322, SEQ ID NO: 1323, SEQ ID NO: 1324, and SEQ ID NO: 1325; SEQ ID NO: 1330, SEQ ID NO: 1331, SEQ ID NO: 1332, SEQ ID NO:

1333, SEQ ID NO: 1334, and SEQ ID NO: 1335; SEQ ID NO: 1340, SEQ ID NO: 1341, SEQ ID NO: 1342, SEQ ID NO: 1343, SEQ ID NO: 1344, and SEQ ID NO: 1345; SEQ ID

NO: 1350, SEQ ID NO: 1351, SEQ ID NO: 1352, SEQ ID NO: 1353, SEQ ID NO: 1354, and SEQ ID NO: 1355; and SEQ ID NO: 1360, SEQ ID NO: 1361, SEQ ID NO: 1362, SEQ ID

NO: 1363, SEQ ID NO: 1364, and SEQ ID NO: 1365.
[0225] In another aspect, an antigen binding protein includes 1, 2, 3, 4, 5, or 6 variant forms of the CDRs listed in TABLES 4A and 4B, each having at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to a CDR sequence listed in TABLES 4A and 4B. Some antigen binding proteins include 1, 2, 3, 4, 5, or 6 of the CDRs listed in TABLES 4A and 4B, each or collectively differing by no more than 1, 2, 3, 4 or 5 amino acids from the CDRs listed in this table.
[0226] In various other embodiments, the antigen binding protein is derived from such antibodies. For instance, in one aspect, the antigen binding protein comprises 1, 2, 3, 4, 5 or all 6 of the CDRs listed in one of the rows for any particular antibody listed in TABLES 4A

and 4B. In another aspect, an antigen binding protein includes 1, 2, 3, 4, 5, or 6 variant forms of the CDRs listed in one of the rows for an antibody in TABLES 4A and 4B, each CDR
having at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to a CDR
sequence listed in TABLES 4A and 4B. Some antigen binding proteins include 1, 2, 3, 4, 5, or 6 of the CDRs listed in one of the rows of TABLES 4A and 4B, each differing by no more than 1, 2, 3, 4 or 5 amino acids from the CDRs listed in these tables. In another aspect, the antigen binding protein comprises all 6 of the CDRS listed in a row of TABLES
4A and 4B
and the total number of amino acid changes to the CDRs collectively is no more than 1, 2, 3, 4, or 5 amino acids.
[0227] In one embodiment the antibody or fragment thereof comprises a light chain comprising a sequence selected from the group consisting of SEQ ID NOs: 963, 967, 971, 975,979,983,987,991,995,999,1003,1007,1011,1015,1019,1023,1027,1031,1035, 1039,1043,1047,1051,1055,1059,1063,1067,1071,1075,1079,1083,1087,1091,1095, 1099, 1103, 1107, 1111, 1115, 1119, 1123, 1127, 1131, 1135, 1139, 1143, 1147, 1151, 1155, 1159, 1163, 1167, 1171, 1175, 1179, 1183, 1187, 1191, 1195, 1199, 1288, 1298, 1308, 1318, 1328, 1338, 1348, and 1358. In one embodiment the antibody or fragment thereof comprises a heavy chain comprising a sequence selected from the group consisting of SEQ
ID NOs:
964, 968, 972, 976, 980, 984, 988, 992, 996, 1000, 1004, 1008, 1012, 1016, 1020, 1024, 1028, 1032, 1036, 1040, 1044, 1048, 1052, 1056, 1060, 1064, 1068, 1072, 1076, 1080, 1084, 1088, 1092, 1096, 1100, 1104, 1108, 1112, 1116, 1120, 1124, 1128, 1132, 1136, 1140, 1144, 1148, 1152, 1156, 1160, 1164, 1168, 1172, 1176, 1180, 1184, 1188, 1192, 1196, 1200, 1289, 1299, 1309, 1319, 1329, 1339, 1349, and 1359. In one embodiment the antibody or fragment thereof comprises a light chain comprising a sequence selected from the group consisting of SEQ ID NOs: 963, 967, 971, 975, 979, 983, 987, 991, 995, 999, 1003, 1007, 1011, 1015, 1019, 1023, 1027, 1031, 1035, 1039, 1043, 1047, 1051, 1055, 1059, 1063, 1067, 1071, 1075, 1079, 1083, 1087, 1091, 1095, 1099, 1103, 1107, 1111, 1115, 1119, 1123, 1127, 1131, 1135, 1139,1143,1147,1151,1155,1159,1163,1167,1171,1175,1179,1183,1187,1191,1195, 1199, 1288, 1298, 1308, 1318, 1328, 1338, 1348, and 1358 and a heavy chain comprising a sequence selected from the group consisting of SEQ ID NOs: 964, 968, 972, 976, 980, 984, 988, 992, 996, 1000, 1004, 1008, 1012, 1016, 1020, 1024, 1028, 1032, 1036, 1040, 1044, 1048, 1052, 1056, 1060, 1064, 1068, 1072, 1076, 1080, 1084, 1088, 1092, 1096, 1100, 1104, 1108, 1112, 1116, 1120, 1124, 1128, 1132, 1136, 1140, 1144, 1148, 1152, 1156, 1160, 1164, 1168, 1172, 1176, 1180, 1184, 1188, 1192, 1196, 1200, 1289, 1299, 1309, 1319, 1329, 1339, 1349, and 1359. In one embodiment the antibody or fragment thereof comprises a combination of a light chain and a heavy chain selected from the group consisting of a light chain comprising SEQ ID NO: 963 and a heavy chain comprising SEQ ID NO: 964; a light chain comprising SEQ ID NO: 967 and a heavy chain comprising SEQ ID NO: 968; a light chain comprising SEQ ID NO: 971 and a heavy chain comprising SEQ ID NO: 972; a light chain comprising SEQ ID NO: 975 and a heavy chain comprising SEQ ID NO: 976; a light chain comprising SEQ ID NO: 979 and a heavy chain comprising SEQ ID NO: 980; a light chain comprising SEQ ID NO: 983 and a heavy chain comprising SEQ ID NO: 984; a light chain comprising SEQ ID NO: 987 and a heavy chain comprising SEQ ID NO: 988; a light chain comprising SEQ ID NO: 991 and a heavy chain comprising SEQ ID NO: 992; a light chain comprising SEQ ID NO: 995 and a heavy chain comprising SEQ ID NO: 996; a light chain comprising SEQ ID NO: 999 and a heavy chain comprising SEQ ID NO: 1000;
a light chain comprising SEQ ID NO: 1003 and a heavy chain comprising SEQ ID NO: 1004;
a light chain comprising SEQ ID NO: 1007 and a heavy chain comprising SEQ ID NO: 1008;
a light chain comprising SEQ ID NO: 1011 and a heavy chain comprising SEQ ID NO: 1012;
a light chain comprising SEQ ID NO: 1015 and a heavy chain comprising SEQ ID NO: 1016;
alight chain comprising SEQ ID NO: 1019 and a heavy chain comprising SEQ ID NO: 1020;
alight chain comprising SEQ ID NO: 1023 and a heavy chain comprising SEQ ID NO: 1024;
a light chain comprising SEQ ID NO: 1027 and a heavy chain comprising SEQ ID NO: 1028;
a light chain comprising SEQ ID NO: 1031 and a heavy chain comprising SEQ ID NO: 1032;
a light chain comprising SEQ ID NO: 1035 and a heavy chain comprising SEQ ID NO: 1036;
a light chain comprising SEQ ID NO: 1039 and a heavy chain comprising SEQ ID NO: 1040;
a light chain comprising SEQ ID NO: 1043 and a heavy chain comprising SEQ ID NO: 1044;
a light chain comprising SEQ ID NO: 1047 and a heavy chain comprising SEQ ID NO: 1048;
a light chain comprising SEQ ID NO: 1051 and a heavy chain comprising SEQ ID NO: 1052;
a light chain comprising SEQ ID NO: 1055 and a heavy chain comprising SEQ ID NO: 1056;
a light chain comprising SEQ ID NO: 1059 and a heavy chain comprising SEQ ID NO: 1060;
a light chain comprising SEQ ID NO: 1063 and a heavy chain comprising SEQ ID NO: 1064;
a light chain comprising SEQ ID NO: 1067 and a heavy chain comprising SEQ ID NO: 1068;
a light chain comprising SEQ ID NO: 1071 and a heavy chain comprising SEQ ID NO: 1072;
a light chain comprising SEQ ID NO: 1075 and a heavy chain comprising SEQ ID NO: 1076;
a light chain comprising SEQ ID NO: 1079 and a heavy chain comprising SEQ ID NO: 1080;
alight chain comprising SEQ ID NO: 1083 and a heavy chain comprising SEQ ID NO: 1084;
a light chain comprising SEQ ID NO: 1087 and a heavy chain comprising SEQ ID NO: 1088;
alight chain comprising SEQ ID NO: 1091 and a heavy chain comprising SEQ ID NO: 1092;
a light chain comprising SEQ ID NO: 1095 and a heavy chain comprising SEQ ID NO: 1096;
a light chain comprising SEQ ID NO: 1099 and a heavy chain comprising SEQ ID NO: 1100;
a light chain comprising SEQ ID NO: 1103 and a heavy chain comprising SEQ ID NO: 1104;
a light chain comprising SEQ ID NO: 1107 and a heavy chain comprising SEQ ID NO: 1108;
a light chain comprising SEQ ID NO: 1111 and a heavy chain comprising SEQ ID NO: 1112;
a light chain comprising SEQ ID NO: 1115 and a heavy chain comprising SEQ ID NO: 1116;
a light chain comprising SEQ ID NO: 1119 and a heavy chain comprising SEQ ID NO: 1120;
a light chain comprising SEQ ID NO: 1123 and a heavy chain comprising SEQ ID NO: 1124;
a light chain comprising SEQ ID NO: 1127 and a heavy chain comprising SEQ ID NO: 1128;
a light chain comprising SEQ ID NO: 1131 and a heavy chain comprising SEQ ID NO: 1132;
a light chain comprising SEQ ID NO: 1135 and a heavy chain comprising SEQ ID NO: 1136;
a light chain comprising SEQ ID NO: 1139 and a heavy chain comprising SEQ ID NO: 1140;
a light chain comprising SEQ ID NO: 1143 and a heavy chain comprising SEQ ID NO: 1144;
a light chain comprising SEQ ID NO: 1147 and a heavy chain comprising SEQ ID NO: 1148;
a light chain comprising SEQ ID NO: 1151 and a heavy chain comprising SEQ ID NO: 1152;
a light chain comprising SEQ ID NO: 1155 and a heavy chain comprising SEQ ID NO: 1156;
a light chain comprising SEQ ID NO: 1159 and a heavy chain comprising SEQ ID NO: 1160;
a light chain comprising SEQ ID NO: 1163 and a heavy chain comprising SEQ ID NO: 1164;
a light chain comprising SEQ ID NO: 1167 and a heavy chain comprising SEQ ID NO: 1168;
a light chain comprising SEQ ID NO: 1171 and a heavy chain comprising SEQ ID NO: 1172;
a light chain comprising SEQ ID NO: 1175 and a heavy chain comprising SEQ ID NO: 1176;
a light chain comprising SEQ ID NO: 1179 and a heavy chain comprising SEQ ID NO: 1180;
a light chain comprising SEQ ID NO: 1183 and a heavy chain comprising SEQ ID NO: 1184;
a light chain comprising SEQ ID NO: 1187 and a heavy chain comprising SEQ ID NO: 1188;
a light chain comprising SEQ ID NO: 1191 and a heavy chain comprising SEQ ID NO: 1192;
a light chain comprising SEQ ID NO: 1195 and a heavy chain comprising SEQ ID NO: 1196;
a light chain comprising SEQ ID NO: 1199 and a heavy chain comprising SEQ ID NO: 1200;
a light chain comprising SEQ ID NO: 1288 and a heavy chain comprising SEQ ID NO: 1289;
a light chain comprising SEQ ID NO: 1298 and a heavy chain comprising SEQ ID NO: 1299;
a light chain comprising SEQ ID NO: 1308 and a heavy chain comprising SEQ ID NO: 1309;
a light chain comprising SEQ ID NO: 1318 and a heavy chain comprising SEQ ID NO: 1319;
a light chain comprising SEQ ID NO: 1328 and a heavy chain comprising SEQ ID NO: 1329;
a light chain comprising SEQ ID NO: 1338 and a heavy chain comprising SEQ ID NO: 1339;
a light chain comprising SEQ ID NO: 1348 and a heavy chain comprising SEQ ID NO: 1349;
and a light chain comprising SEQ ID NO: 1358 and a heavy chain comprising SEQ ID NO:
1359.
[0228] In one embodiment the antibody or fragment thereof comprises a light chain encoded by a polynucleotide sequence selected from the group consisting of SEQ ID NOs:
961, 965, 969, 973, 977, 981, 985, 989, 993, 997, 1001, 1005, 1009, 1013, 1017, 1021, 1025, 1029, 1033,1037,1041,1045,1049,1053,1057,1061,1065,1069,1073,1077,1081,1085,1089, 1093,1097,1101,1105,1109,1113,1117,1121,1125,1129,1133,1137,1141,1145,1149, 1153,1157,1161,1165,1169,1173,1177,1181,1185,1189,1193,1197,1361,1363,1365, 1367, 1369, 1371, 1373, and 1375. In one embodiment the antibody or fragment thereof comprises a heavy chain encoded by a polynucleotide sequence selected from the group consisting of SEQ ID NOs: 962, 966, 970, 974, 978, 982, 986, 990, 994, 998, 1002, 1006, 1010, 1014, 1018, 1022, 1026, 1030, 1034, 1038, 1042, 1046, 1050, 1054, 1058, 1062, 1066, 1070, 1074, 1078, 1082, 1086, 1090, 1094, 1098, 1102, 1106, 1110, 1114, 1118, 1122, 1126, 1130, 1134, 1138, 1142, 1146, 1150, 1154, 1158, 1162, 1166, 1170, 1174, 1178, 1182, 1186, 1190, 1194, 1198, 1362, 1364, 1366, 1368, 1370, 1372, 1374, and 1376. In one embodiment the antibody or fragment thereof comprises a light chain encoded by a polynucleotide sequence selected from the group consisting of SEQ ID NOs: 961, 965, 969, 973, 977, 981, 985,989,993,997,1001,1005,1009,1013,1017,1021,1025,1029,1033,1037,1041, 1045,1049,1053,1057,1061,1065,1069,1073,1077,1081,1085,1089,1093,1097,1101, 1105, 1109, 1113, 1117, 1121, 1125, 1129, 1133, 1137, 1141, 1145, 1149, 1153, 1157, 1161, 1165, 1169, 1173, 1177, 1181, 1185, 1189, 1193, 1197, 1361, 1363, 1365, 1367, 1369, 1371, 1373, and 1375 and a heavy chain comprising a sequence selected from the group consisting of SEQ ID NOs: 962, 966, 970, 974, 978, 982, 986, 990, 994, 998, 1002, 1006, 1010, 1014, 1018, 1022, 1026, 1030, 1034, 1038, 1042, 1046, 1050, 1054, 1058, 1062, 1066, 1070, 1074, 1078, 1082, 1086, 1090, 1094, 1098, 1102, 1106, 1110, 1114, 1118, 1122, 1126, 1130, 1134, 1138, 1142, 1146, 1150, 1154, 1158, 1162, 1166, 1170, 1174, 1178, 1182, 1186, 1190, 1194, 1198, 1362, 1364, 1366, 1368, 1370, 1372, 1374, and 1376. In one embodiment the antibody or fragment thereof comprises a combination of light chain variable region and a heavy chain variable region selected from the group consisting of a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 961 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 962; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 965 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 966; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 969 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 970; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 973 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 974; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 977 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 978; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 981 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 982; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 985 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 986; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 989 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 990; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 993 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 994; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 997 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 998; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1001 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1002; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1005 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1006; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1009 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1010; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1013 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1014; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1017 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1018; alight chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1021 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1022; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1025 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1026; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1029 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1030; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1033 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1034; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1037 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1038; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1041 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1042; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1045 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1046; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1049 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1050; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1053 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1054; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1057 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1058; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1061 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1062; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1065 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1066; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1069 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1070; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1073 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1074; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1077 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1078; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1081 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1082; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1085 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1086; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1089 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1090; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1093 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1094; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1097 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1098; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1101 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1102; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1105 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1106; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1109 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1110; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1113 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1114; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1117 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1118; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1121 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1122; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1125 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1126; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1129 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1130; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1133 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1134; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1137 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1138; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1141 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1142; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1145 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1146; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1149 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1150; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1153 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1154; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1157 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1158; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1161 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1162; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1165 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1166; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1169 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1170; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1173 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1174; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1177 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1178; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1181 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1182; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1185 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1186; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1189 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1190; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1193 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1194; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1197 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1198; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1361 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1362; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1363 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1364; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1365 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1366; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1367 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1368; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1369 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1370; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1371 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1372; a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1373 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1374; and a light chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1375 and a heavy chain encoded by a polynucleotide sequence comprising SEQ ID NO: 1376.
[0229] In some aspects, the invention comprises an antibody that binds to GIPR, wherein the antibody binds to GIPR and reduces the likelihood that GIPR binds to GIP.
[0230] In another aspect, the antigen binding protein comprises a full length light chain and a full length heavy chain as listed in one of the rows for one of the antibodies listed in TABLE
5. Some antigen binding proteins that are provided comprise a full length light chain and a full length heavy chain as listed in one of the rows for one of the antibodies listed in TABLE
5, except that one or both of the chains differs from the sequence specified in the table at only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 amino acid residues, wherein each such sequence difference is independently either a single amino acid deletion, insertion or substitution, with the deletions, insertions and/or substitutions resulting in no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 amino acid changes relative to the full length sequences specified in TABLE 5. In one embodiment the antigen binding protein comprises a full length light chain and/or a full length heavy chain from Table 5 with the N-terminal methionine deleted. In one embodiment the antigen binding protein comprises a full length light chain and/or a full length heavy chain from Table 5 with the C-terminal lysine deleted.
Other antigen binding proteins also comprise a full length light chain and a full length heavy chain as listed in one of the rows for one of the antibodies listed in TABLE
5, except that one or both of the chains differs from the sequence specified in the table in that the light chain and/or heavy chain comprises or consists of a sequence of amino acids that has at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequences of the light chain or heavy chain sequences as specified in TABLE S.
[0231] In another embodiment, the antigen binding protein consists of a just a light or a heavy chain polypeptide as set forth in TABLE S.
[0232] In still another aspect, antigen-binding proteins containing the CDRs, variable domains and/or full length sequences listed in TABLES 3, 4A, 4B, and 5 is a monoclonal antibody, a chimeric antibody, a humanized antibody, a human antibody, a multispecific antibody, or an antibody fragment of the foregoing. In another embodiment, the antibody fragment of the isolated antigen-binding proteins provided herein is a Fab fragment, a Fab' fragment, an F(ab1)2 fragment, an Fv fragment, a diabody, or a scFv based upon an antibody with the sequences as listed in TABLE S.
[0233] In yet another aspect, the isolated antigen-binding protein provided in TABLE 5 can be coupled to a labeling group and can compete for binding to GIPR with an antigen binding protein of one of the isolated antigen-binding proteins provided herein.
[0234] In another embodiment, antigen binding proteins are provided that compete with one of the exemplified antibodies or functional fragments described above for specific binding to a human GIPR (e.g., SEQ ID NO: 1201). Such antigen binding proteins may bind to the same epitope as one of the antigen binding proteins described herein, or to an overlapping epitope.
Antigen binding proteins and fragments that compete with the exemplified antigen binding proteins are expected to show similar functional properties. The exemplified antigen binding proteins and fragments include those described above, including those with heavy and light chains, variable region domains and CDRs included in TABLES 3, 4A, 4B, and 5.
Thus, as a specific example, the antigen binding proteins that are provided include those that compete with an antibody having:
[0235] all 6 of the CDRs listed for any antibody listed in TABLES 4A and 4B;
[0236] a VH and a VL listed for any antibody listed in TABLE 3; or [0237] two light chains and two heavy chains as specified for any antibody listed in TABLE
5.
[0238] The antigen binding proteins that are provided include monoclonal antibodies that bind to GIPR. Monoclonal antibodies may be produced using any technique known in the art, e.g., by immortalizing spleen cells harvested from the transgenic animal after completion of the immunization schedule. The spleen cells can be immortalized using any technique known in the art, e.g., by fusing them with myeloma cells to produce hybridomas.
Myeloma cells for use in hybridoma-producing fusion procedures preferably are non-antibody-producing, have high fusion efficiency, and enzyme deficiencies that render them incapable of growing in certain selective media which support the growth of only the desired fused cells (hybridomas). Examples of suitable cell lines for use in mouse fusions include Sp-20, P3-X63/Ag8, P3-X63-Ag8.653, NS1/1.Ag 4 1, 5p210-Ag14, FO, NSO/U, MPC-11, MPC11-X45-GTG 1.7 and 5194/5XXO Bul; examples of cell lines used in rat fusions include R210.RCY3, Y3-Ag 1.2.3, IR983F and 4B210. Other cell lines useful for cell fusions are U-266, GM1500-GRG2, LICR-LON-HMy2 and UC729-6.
[0239] In some instances, a hybridoma cell line is produced by immunizing an animal (e.g., a transgenic animal having human immunoglobulin sequences) with a GIPR
immunogen;
harvesting spleen cells from the immunized animal; fusing the harvested spleen cells to a myeloma cell line, thereby generating hybridoma cells; establishing hybridoma cell lines from the hybridoma cells, and identifying a hybridoma cell line that produces an antibody that binds a GIPR polypeptide. Such hybridoma cell lines, and anti-GIPR
monoclonal antibodies produced by them, are aspects of the present application.
[0240] Monoclonal antibodies secreted by a hybridoma cell line can be purified using any technique known in the art. Hybridomas or mAbs may be further screened to identify mAbs with particular properties, such as the ability to increase GIPR activity.
[0241] Chimeric and humanized antibodies based upon the foregoing sequences are also provided. Monoclonal antibodies for use as therapeutic agents may be modified in various ways prior to use. One example is a chimeric antibody, which is an antibody composed of protein segments from different antibodies that are covalently joined to produce functional immunoglobulin light or heavy chains or immunologically functional portions thereof Generally, a portion of the heavy chain and/or light chain is identical with or homologous to a corresponding sequence in antibodies derived from a particular species or belonging to a particular antibody class or subclass, while the remainder of the chain(s) is/are identical with or homologous to a corresponding sequence in antibodies derived from another species or belonging to another antibody class or subclass. For methods relating to chimeric antibodies, see, for example, United States Patent No. 4,816,567; and Morrison etal., 1985, Proc. Natl.
Acad. Sci. USA 81:6851-6855, which are hereby incorporated by reference. CDR
grafting is described, for example, in United States Patent No. 6,180,370, No. 5,693,762, No. 5,693,761, No. 5,585,089, and No. 5,530,101.
[0242] Generally, the goal of making a chimeric antibody is to create a chimera in which the number of amino acids from the intended patient species is maximized. One example is the "CDR-grafted" antibody, in which the antibody comprises one or more complementarity determining regions (CDRs) from a particular species or belonging to a particular antibody class or subclass, while the remainder of the antibody chain(s) is/are identical with or homologous to a corresponding sequence in antibodies derived from another species or belonging to another antibody class or subclass. For use in humans, the variable region or selected CDRs from a rodent antibody often are grafted into a human antibody, replacing the naturally-occurring variable regions or CDRs of the human antibody.
[0243] One useful type of chimeric antibody is a "humanized" antibody.
Generally, a humanized antibody is produced from a monoclonal antibody raised initially in a non-human animal. Certain amino acid residues in this monoclonal antibody, typically from non-antigen recognizing portions of the antibody, are modified to be homologous to corresponding residues in a human antibody of corresponding isotype. Humanization can be performed, for example, using various methods by substituting at least a portion of a rodent variable region for the corresponding regions of a human antibody (see, e.g., United States Patent No.
5,585,089, and No. 5,693,762; Jones etal., 1986, Nature 321:522-525; Riechmann etal., 1988, Nature 332:323-27; Verhoeyen etal., 1988, Science 239:1534-1536).
[0244] In one aspect, the CDRs of the light and heavy chain variable regions of the antibodies provided herein are grafted to framework regions (FRs) from antibodies from the same, or a different, phylogenetic species. For example, the CDRs of the heavy and light chain variable regions VH1, VH2, VH3, VH4, VHS, VH6, VH7, VH8, VH9, VH10, VH11, VH12 and/or VL1, and VL2 can be grafted to consensus human FRs. To create consensus human FRs, FRs from several human heavy chain or light chain amino acid sequences may be aligned to identify a consensus amino acid sequence. In other embodiments, the FRs of a heavy chain or light chain disclosed herein are replaced with the FRs from a different heavy chain or light chain. In one aspect, rare amino acids in the FRs of the heavy and light chains of GIPR antibodies are not replaced, while the rest of the FR amino acids are replaced. A
"rare amino acid" is a specific amino acid that is in a position in which this particular amino acid is not usually found in an FR. Alternatively, the grafted variable regions from the one heavy or light chain may be used with a constant region that is different from the constant region of that particular heavy or light chain as disclosed herein. In other embodiments, the grafted variable regions are part of a single chain FAT antibody.
[0245] In certain embodiments, constant regions from species other than human can be used along with the human variable region(s) to produce hybrid antibodies.
[0246] Fully human GIPR antibodies are also provided. Methods are available for making fully human antibodies specific for a given antigen without exposing human beings to the antigen ("fully human antibodies"). One specific means provided for implementing the production of fully human antibodies is the "humanization" of the mouse humoral immune system. Introduction of human immunoglobulin (Ig) loci into mice in which the endogenous Ig genes have been inactivated is one means of producing fully human monoclonal antibodies (mAbs) in mouse, an animal that can be immunized with any desirable antigen.
Using fully human antibodies can minimize the immunogenic and allergic responses that can sometimes be caused by administering mouse or mouse-derived mAbs to humans as therapeutic agents.
[0247] Fully human antibodies can be produced by immunizing transgenic animals (usually mice) that are capable of producing a repertoire of human antibodies in the absence of endogenous immunoglobulin production. Antigens for this purpose typically have six or more contiguous amino acids, and optionally are conjugated to a carrier, such as a hapten. See, e.g., Jakobovits etal., 1993, Proc. Natl. Acad. Sci. USA 90:2551-2555; Jakobovits etal., 1993, Nature 362:255-258; and Bruggermann etal., 1993, Year in Immunol. 7:33. In one example of such a method, transgenic animals are produced by incapacitating the endogenous mouse immunoglobulin loci encoding the mouse heavy and light immunoglobulin chains therein, and inserting into the mouse genome large fragments of human genome DNA
containing loci that encode human heavy and light chain proteins. Partially modified animals, which have less than the full complement of human immunoglobulin loci, are then cross-bred to obtain an animal having all of the desired immune system modifications. When administered an immunogen, these transgenic animals produce antibodies that are immunospecific for the immunogen but have human rather than murine amino acid sequences, including the variable regions. For further details of such methods, see, for example, W096/33735 and W094/02602. Additional methods relating to transgenic mice for making human antibodies are described in United States Patent No. 5,545,807; No. 6,713,610; No.
6,673,986;
No. 6,162,963; No. 5,545,807; No. 6,300,129; No. 6,255,458; No. 5,877,397; No.
5,874,299 and No. 5,545,806; in PCT publications W091/10741, W090/04036, and in EP

and EP 546073A1.
[0248] The transgenic mice described above, referred to herein as "HuMab"
mice, contain a human immunoglobulin gene minilocus that encodes unrearranged human heavy ([mu] and [gamma]) and [kappa] light chain immunoglobulin sequences, together with targeted mutations that inactivate the endogenous [mu] and [kappa] chain loci (Lonberg et al., 1994, Nature 368:856-859). Accordingly, the mice exhibit reduced expression of mouse IgM or [kappa] and in response to immunization, and the introduced human heavy and light chain transgenes undergo class switching and somatic mutation to generate high affinity human IgG
[kappa] monoclonal antibodies (Lonberg etal., supra.; Lonberg and Huszar, 1995, Intern.
Rev. Immunol. 13: 65-93; Harding and Lonberg, 1995, Ann. NY Acad. Sci. 764:536-546).
The preparation of HuMab mice is described in detail in Taylor et al., 1992, Nucleic Acids Research 20:6287-6295; Chen etal., 1993, International Immunology 5:647-656;
Tuaillon et al., 1994,1 Immunol. 152:2912-2920; Lonberg etal., 1994, Nature 368:856-859;
Lonberg, 1994, Handbook of Exp. Pharmacology 113:49-101; Taylor etal., 1994, International Immunology 6:579-591; Lonberg and Huszar, 1995, Intern. Rev. Immunol. 13:65-93; Harding and Lonberg, 1995, Ann. NY Acad. Sci. 764:536-546; Fishwild etal., 1996, Nature Biotechnology 14:845-851; the foregoing references are hereby incorporated by reference in their entirety for all purposes. See, further United States Patent No.
5,545,806; No. 5,569,825;
No. 5,625,126; No. 5,633,425; No. 5,789,650; No. 5,877,397; No. 5,661,016; No.
5,814,318;
No. 5,874,299; and No. 5,770,429; as well as United States Patent No.
5,545,807;
International Publication Nos. WO 93/1227; WO 92/22646; and WO 92/03918, the disclosures of all of which are hereby incorporated by reference in their entirety for all purposes. Technologies utilized for producing human antibodies in these transgenic mice are disclosed also in WO 98/24893, and Mendez etal., 1997, Nature Genetics 15:146-156, which are hereby incorporated by reference. For example, the HCo7 and HCo12 transgenic mice strains can be used to generate human monoclonal antibodies against GIPR.
Further details regarding the production of human antibodies using transgenic mice are provided below.

[0249] Using hybridoma technology, antigen-specific human mAbs with the desired specificity can be produced and selected from the transgenic mice such as those described above. Such antibodies may be cloned and expressed using a suitable vector and host cell, or the antibodies can be harvested from cultured hybridoma cells.
[0250] Fully human antibodies can also be derived from phage-display libraries (as disclosed in Hoogenboom etal., 1991, 1 Mol. Biol. 227:381; and Marks et al., 1991, 1 Mol. Biol.
222:581). Phage display techniques mimic immune selection through the display of antibody repertoires on the surface of filamentous bacteriophage, and subsequent selection of phage by their binding to an antigen of choice. One such technique is described in PCT
Publication No.
WO 99/10494 (hereby incorporated by reference).
[0251] The GIPR binding protein can also be a variant, mimetic, derivative or oligomer based upon the structure of GIPR antigen binding proteins have the CDRs, variable regions and/or full length chains as described above.
[0252] In one embodiment, for instance, an antigen binding protein is a variant form of the antigen binding proteins disclosed above. For instance, some of the antigen binding proteins have one or more conservative amino acid substitutions in one or more of the heavy or light chains, variable regions or CDRs.
[0253] Naturally-occurring amino acids may be divided into classes based on common side chain properties:
[0254] 1) hydrophobic: norleucine, Met, Ala, Val, Leu, Ile;
[0255] 2) neutral hydrophilic: Cys, Ser, Thr, Asn, Gln;
[0256] 3) acidic: Asp, Glu;
[0257] 4) basic: His, Lys, Arg;
[0258] 5) residues that influence chain orientation: Gly, Pro; and [0259] 6) aromatic: Trp, Tyr, Phe.
[0260] Conservative amino acid substitutions may involve exchange of a member of one of these classes with another member of the same class. Conservative amino acid substitutions may encompass non-naturally occurring amino acid residues, which are typically incorporated by chemical peptide synthesis rather than by synthesis in biological systems.
These include peptidomimetics and other reversed or inverted forms of amino acid moieties.
[0261] Non-conservative substitutions may involve the exchange of a member of one of the above classes for a member from another class. Such substituted residues may be introduced into regions of the antibody that are homologous with human antibodies, or into the non-homologous regions of the molecule.

[0262] In making such changes, according to certain embodiments, the hydropathic index of amino acids may be considered. The hydropathic profile of a protein is calculated by assigning each amino acid a numerical value ("hydropathy index") and then repetitively averaging these values along the peptide chain. Each amino acid has been assigned a hydropathic index on the basis of its hydrophobicity and charge characteristics. They are:
isoleucine (+4.5); valine (+4.2); leucine (+3.8); phenylalanine (+2.8);
cysteine/cystine (+2.5);
methionine (+1.9); alanine (+1.8); glycine (-0.4); threonine (-0.7); serine (-0.8); tryptophan (-0.9); tyrosine (-1.3); proline (-1.6); histidine (-3.2); glutamate (-3.5);
glutamine (-3.5);
aspartate (-3.5); asparagine (-3.5); lysine (-3.9); and arginine (-4.5).
[0263] The importance of the hydropathic profile in conferring interactive biological function on a protein is understood in the art (see, e.g., Kyte et al., 1982, 1 Mol.
Biol. 157:105-131). It is known that certain amino acids may be substituted for other amino acids having a similar hydropathic index or score and still retain a similar biological activity. In making changes based upon the hydropathic index, in certain embodiments, the substitution of amino acids whose hydropathic indices are within 2 is included. In some aspects, those which are within 1 are included, and in other aspects, those within 0.5 are included.
[0264] It is also understood in the art that the substitution of like amino acids can be made effectively on the basis of hydrophilicity, particularly where the biologically functional protein or peptide thereby created is intended for use in immunological embodiments, as in the present case. In certain embodiments, the greatest local average hydrophilicity of a protein, as governed by the hydrophilicity of its adjacent amino acids, correlates with its immunogenicity and antigen-binding or immunogenicity, that is, with a biological property of the protein.
[0265] The following hydrophilicity values have been assigned to these amino acid residues:
arginine (+3.0); lysine (+3.0); aspartate (+3.0 1); glutamate (+3.0 1); serine (+0.3);
asparagine (+0.2); glutamine (+0.2); glycine (0); threonine (-0.4); proline (-0.5 1); alanine (-0.5); histidine (-0.5); cysteine (-1.0); methionine (-1.3); valine (-1.5);
leucine (-1.8);
isoleucine (-1.8); tyrosine (-2.3); phenylalanine (-2.5) and tryptophan (-3.4). In making changes based upon similar hydrophilicity values, in certain embodiments, the substitution of amino acids whose hydrophilicity values are within 2 is included, in other embodiments, those which are within 1 are included, and in still other embodiments, those within 0.5 are included. In some instances, one may also identify epitopes from primary amino acid sequences on the basis of hydrophilicity. These regions are also referred to as "epitopic core regions."

[0266] Exemplary conservative amino acid substitutions are set forth in Table 6.
Table 8: Conservative Amino Acid Substitutions Original Residue Exemplary Substitutions Ala Ser Arg Lys Asn Gln, His Asp Glu Cys Ser Gln Asn Glu Asp Gly Pro His Asn, Gln Ile Leu, Val Leu Ile, Val Lys Arg, Gln, Glu Met Leu, Ile Phe Met, Leu, Tyr Ser Thr Thr Ser Trp Tyr Tyr Trp, Phe Val Ile, Leu [0267] A skilled artisan will be able to determine suitable variants of polypeptides as set forth herein using well-known techniques. One skilled in the art may identify suitable areas of the molecule that may be changed without destroying activity by targeting regions not believed to be important for activity. The skilled artisan also will be able to identify residues and portions of the molecules that are conserved among similar polypeptides. In further embodiments, even areas that may be important for biological activity or for structure may be subject to conservative amino acid substitutions without destroying the biological activity or without adversely affecting the polypeptide structure.
[0268] Additionally, one skilled in the art can review structure-function studies identifying residues in similar polypeptides that are important for activity or structure.
In view of such a DEMANDE OU BREVET VOLUMINEUX
LA PRESENTE PARTIE DE CETTE DEMANDE OU CE BREVET COMPREND
PLUS D'UN TOME.

NOTE : Pour les tomes additionels, veuillez contacter le Bureau canadien des brevets JUMBO APPLICATIONS/PATENTS
THIS SECTION OF THE APPLICATION/PATENT CONTAINS MORE THAN ONE
VOLUME

NOTE: For additional volumes, please contact the Canadian Patent Office NOM DU FICHIER / FILE NAME:
NOTE POUR LE TOME / VOLUME NOTE:

Claims (66)

What is claimed is:

1. A method of treating a subject with a metabolic disorder, the method comprising administering to the subject a therapeutically effective amount of an antigen binding protein that specifically binds to a protein having an amino acid sequence having at least 90% amino acid sequence identity to an amino acid sequence of a GIPR.

2. The method of claim 1, wherein said metabolic disorder is a disorder of glucose metabolism.

3. The method of claim 2, wherein said glucose metabolism disorder comprises hyperglycemia and wherein said administering reduces plasma glucose in said subject.

4. The method of claim 2, wherein said glucose metabolism disorder comprises hyperinsulinemia and wherein said administering reduces plasma insulin in said subject.

5. The method of claim 2, wherein said glucose metabolism disorder comprises glucose intolerance and wherein said administering increases glucose tolerance in said subject.

6. The method of claim 2, wherein said glucose metabolism disorder comprises insulin resistance and wherein said administering decreases insulin resistance in said subject.

7. The method of claim 2, wherein said glucose metabolism disorder comprises diabetes mellitus.

8. The method of claim 2, wherein said subject is obese.

9. The method of claim 8, wherein said administering reduces body weight in said subject.

10. The method of claim 8, wherein said administering reduces body weight gain in said subject.

11. The method of claim 8, where said administering reduces fat mass in said subject.

12. The method of claim 8, wherein said glucose metabolism disorder comprises insulin resistance and wherein said administering reduces insulin resistance in said subject.

13. The method of claim 8, where said subject has increased liver steatosis, and wherein said administering reduces liver steatosis in said subject.

14. The method of claim 8, where said subject has increased liver fat content, and wherein said administering reduces liver fat content in said subject.

15. The method of claim 1, wherein said subject is a mammal.

16. The method of claim 1, wherein said subject is human.

17. The method of claim 1, wherein said administering is by parenteral injection.

18. The method of claim 1, wherein said administering is by subcutaneous injection.

19. An isolated antigen binding protein that specifically binds to a human gastric inhibitory peptide receptor (GIPR) polypeptide.

20. The isolated antigen binding protein of claim 19, wherein said human GIPR
has a sequence comprising a sequence selected from the group consisting of SEQ
ID NO:
1201, SEQ ID NO: 1203, and SEQ ID NO: 1205.

21. The isolated antigen binding protein of claim 20, wherein said antigen binding protein is a monoclonal antibody, a polyclonal antibody, a recombinant antibody, a human antibody, a humanized antibody, a chimeric antibody, a multispecific antibody, or an antibody fragment thereof

22. The isolated antigen binding protein of claim 21, wherein said antibody fragment is a Fab fragment, a Fab' fragment, or a F(ab')2 fragment.

23. The isolated antigen binding protein of claim 21, wherein said antigen binding protein is a human antibody.

24. The isolated antigen binding protein of claim 21, wherein said antigen binding protein is a monoclonal antibody.

25. The isolated antigen binding protein of claim 21, wherein said antigen binding protein is of the IgG1-, IgG2- IgG3- or IgG4-type.

26. The isolated antigen binding protein of claim 25, wherein said antigen binding protein is of the IgG1- or the IgG2-type.

27. The isolated antigen binding protein of any of claim 21, wherein said antigen binding protein is coupled to a labeling group.

28. The isolated antigen binding protein of one of claim 21, wherein said antigen binding protein inhibits binding of GIP to the extracellular portion of human GIPR.

29. The isolated antigen binding protein of claim 21, wherein said antigen binding protein is an antibody or a fragment thereof, and wherein said antibody comprises a CDRL1, a CDRL2, a CDRL3, a CDRH1, a CDRH2, and a CDRH3, wherein said CDRL1 comprises a sequence selected from the group consisting of SEQ ID NOs: 4, 10, 16, 22, 28, 34, 40, 46, 52, 58, 64, 70, 76, 82, 88, 94, 100, 106, 112, 118, 124, 130, 136, 142, 148, 154, 160, 166, 172, 178, 184, 190, 196, 202, 208, 214, 220, 226, 232, 238, 244, 250, 256, 262, 268, 274, 280, 286, 292, 298, 304, 310, 316, 322, 328, 334, 340, 346, 352, 358, 1290, 1300, 1310, 1320, 1330, 1340, and 1350; said CDRL2 comprises a sequence selected from the group consisting of SEQ ID NOs: 5, 11, 17, 23, 29, 35, 41, 47, 53, 59, 65, 71, 77, 83, 89, 95, 101, 107, 113, 119, 125, 131, 137, 143, 149, 155, 161, 167, 173, 179, 185, 191, 197, 203, 209, 215, 221, 227, 233, 239, 245, 251, 257, 263, 269, 275, 281, 287, 293, 299, 305, 311, 317, 323, 329, 335, 341, 347, 353, 359, 1291, 1301, 1311, 1321, 1331, 1341, and 1351; said comprises a sequence selected from the group consisting of SEQ ID NOs: 6, 12, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, 102, 108, 114, 120, 126, 132, 138, 144, 150, 156, 162, 168, 174, 180, 186, 192, 198, 204, 210, 216, 222, 228, 234, 240, 246, 252, 258, 264, 270, 276, 282, 288, 294, 300, 306, 312, 318, 324, 330, 336, 342, 348, 354, 360, 1292, 1302, 1312, 1322, 1332, 1342, and 1352; said CDRH1 comprises a sequence selected from the group consisting of SEQ ID NOs: 364, 370, 376, 382, 388, 394, 400, 406, 412, 418, 424, 430, 436, 442, 448, 454, 460, 466, 472, 478, 484, 490, 496, 502, 508, 514, 520, 526, 532, 538, 544, 550, 556, 562, 568, 574, 580, 586, 592, 598, 604, 610, 616, 622, 628, 634, 640, 646, 652, 658, 664, 670, 676, 682, 688, 694, 700, 706, 712, 718, 1293, 1303, 1313, 1323, 1333, 1343, and 1353; said CDRH2 comprises a sequence selected from the group consisting of SEQ ID NOs: 365, 371, 377, 383, 389, 395, 401, 407, 413, 419, 425, 431, 437, 443, 449, 455, 461, 467, 473, 479, 485, 491, 497, 503, 509, 515, 521, 527, 533, 539, 545, 551, 557, 563, 569, 575, 581, 587, 593, 599, 605, 611, 617, 623, 629, 635, 641, 647, 653, 659, 665, 671, 677, 683, 689, 695, 701, 707, 713, 719, 1294, 1304, 1314, 1324, 1334, 1344, and 1354; and said CDRH3 comprises a sequence selected from the group consisting of SEQ ID
NOs: 366, 372, 378, 384, 390, 396, 402, 408, 414, 420, 426, 432, 438, 444, 450, 456, 462, 468, 474, 480, 486, 492, 498, 504, 510, 516, 522, 528, 534, 540, 546, 552, 558, 564, 570, 576, 582, 588, 594, 600, 606, 612, 618, 624, 630, 636, 642, 648, 654, 660, 666, 672, 678, 684, 690, 696, 702, 708, 714, 720, 1295, 1305, 1315, 1325, 1335, 1345, and 1355.

30. The isolated antigen binding protein of claim 21, wherein said antigen binding protein is an antibody or a fragment thereof, and wherein said antibody comprises a CDRL1, a CDRL2, a CDRL3, a CDRH1, a CDRH2, and a CDRH3, wherein each CDRL1, CDRL2, CDRL3, CDRH1, CDRH2, and CDRH3, respectively, comprises a sequence selected from the group consisting of SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO:
364, SEQ ID NO: 365, and SEQ ID NO: 366; SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO:
12, SEQ ID NO: 370, SEQ ID NO: 371, and SEQ ID NO: 372; SEQ ID NO: 16, SEQ ID NO:
17, SEQ ID NO: 18, SEQ ID NO: 376, SEQ ID NO: 377, and SEQ ID NO: 378; SEQ ID NO:
22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 382, SEQ ID NO: 383, and SEQ ID NO:
384;
SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 388, SEQ ID NO: 389, and SEQ ID NO: 390; SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 394, SEQ
ID NO: 395, and SEQ ID NO: 396; SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ
ID NO: 400, SEQ ID NO: 401, and SEQ ID NO: 402; SEQ ID NO: 46, SEQ ID NO: 47, SEQ
ID NO: 48, SEQ ID NO: 406, SEQ ID NO: 407, and SEQ ID NO: 408; SEQ ID NO: 52, SEQ
ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 412, SEQ ID NO: 413, and SEQ ID NO: 414;
SEQ
ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 418, SEQ ID NO: 419, and SEQ
ID NO: 420; SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 424, SEQ
ID
NO: 425, and SEQ ID NO: 426; SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ
ID
NO: 430, SEQ ID NO: 431, and SEQ ID NO: 432; SEQ ID NO: 76, SEQ ID NO: 77, SEQ
ID
NO: 78, SEQ ID NO: 436, SEQ ID NO: 437, and SEQ ID NO: 438; SEQ ID NO: 82, SEQ
ID
NO: 83, SEQ ID NO: 84, SEQ ID NO: 442, SEQ ID NO: 443, and SEQ ID NO: 444; SEQ
ID
NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 448, SEQ ID NO: 449, and SEQ
ID
NO: 450; SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 454, SEQ ID
NO:
455, and SEQ ID NO: 456; SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ
ID
NO: 460, SEQ ID NO: 461, and SEQ ID NO: 462; SEQ ID NO: 106, SEQ ID NO: 107, SEQ
ID NO: 108, SEQ ID NO: 466, SEQ ID NO: 467, and SEQ ID NO: 468; SEQ ID NO:
112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 472, SEQ ID NO: 473, and SEQ ID NO:

474; SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO: 478, SEQ ID
NO:
479, and SEQ ID NO: 480; SEQ ID NO: 124, SEQ ID NO: 125, SEQ ID NO: 126, SEQ
ID
NO: 484, SEQ ID NO: 485, and SEQ ID NO: 486; SEQ ID NO: 130, SEQ ID NO: 131, SEQ
ID NO: 132, SEQ ID NO: 490, SEQ ID NO: 491, and SEQ ID NO: 492; SEQ ID NO:
136, SEQ ID NO: 137, SEQ ID NO: 138, SEQ ID NO: 496, SEQ ID NO: 497, and SEQ ID NO:

498; SEQ ID NO: 142, SEQ ID NO: 143, SEQ ID NO: 144, SEQ ID NO: 502, SEQ ID
NO:
503, and SEQ ID NO: 504; SEQ ID NO: 148, SEQ ID NO: 149, SEQ ID NO: 150, SEQ
ID
NO: 508, SEQ ID NO: 509, and SEQ ID NO: 510; SEQ ID NO: 154, SEQ ID NO: 155, SEQ
ID NO: 156, SEQ ID NO: 514, SEQ ID NO: 515, and SEQ ID NO: 516; SEQ ID NO:
160, SEQ ID NO: 161, SEQ ID NO: 162, SEQ ID NO: 520, SEQ ID NO: 521, and SEQ ID NO:

522; SEQ ID NO: 166, SEQ ID NO: 167, SEQ ID NO: 168, SEQ ID NO: 526, SEQ ID
NO:
527, and SEQ ID NO: 528; SEQ ID NO: 172, SEQ ID NO: 173, SEQ ID NO: 174, SEQ
ID
NO: 532, SEQ ID NO: 533, and SEQ ID NO: 534; SEQ ID NO: 178, SEQ ID NO: 179, SEQ
ID NO: 180, SEQ ID NO: 538, SEQ ID NO: 539, and SEQ ID NO: 540; SEQ ID NO:
184, SEQ ID NO: 185, SEQ ID NO: 186, SEQ ID NO: 544, SEQ ID NO: 545, and SEQ ID NO:

546; SEQ ID NO: 190, SEQ ID NO: 191, SEQ ID NO: 192, SEQ ID NO: 550, SEQ ID
NO:
551, and SEQ ID NO: 552; SEQ ID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ
ID
NO: 556, SEQ ID NO: 557, and SEQ ID NO: 558; SEQ ID NO: 202, SEQ ID NO: 203, SEQ
ID NO: 204, SEQ ID NO: 562, SEQ ID NO: 563, and SEQ ID NO: 564; SEQ ID NO:
208, SEQ ID NO: 209, SEQ ID NO: 210, SEQ ID NO: 568, SEQ ID NO: 569, and SEQ ID NO:

570; SEQ ID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 574, SEQ ID
NO:
575, and SEQ ID NO: 576; SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ
ID
NO: 580, SEQ ID NO: 581, and SEQ ID NO: 582; SEQ ID NO: 226, SEQ ID NO: 227, SEQ
ID NO: 228, SEQ ID NO: 586, SEQ ID NO: 587, and SEQ ID NO: 588; SEQ ID NO:
232, SEQ ID NO: 233, SEQ ID NO: 234, SEQ ID NO: 592, SEQ ID NO: 593, and SEQ ID NO:

594; SEQ ID NO: 238, SEQ ID NO: 239, SEQ ID NO: 240, SEQ ID NO: 598, SEQ ID
NO:
599, and SEQ ID NO: 600; SEQ ID NO: 244, SEQ ID NO: 245, SEQ ID NO: 246, SEQ
ID
NO: 604, SEQ ID NO: 605, and SEQ ID NO: 606; SEQ ID NO: 250, SEQ ID NO: 251, SEQ
ID NO: 252, SEQ ID NO: 610, SEQ ID NO: 611, and SEQ ID NO: 612; SEQ ID NO:
256, SEQ ID NO: 257, SEQ ID NO: 258, SEQ ID NO: 616, SEQ ID NO: 617, and SEQ ID NO:

618; SEQ ID NO: 262, SEQ ID NO: 263, SEQ ID NO: 264, SEQ ID NO: 622, SEQ ID
NO:
623, and SEQ ID NO: 624; SEQ ID NO: 268, SEQ ID NO: 269, SEQ ID NO: 270, SEQ
ID
NO: 628, SEQ ID NO: 629, and SEQ ID NO: 630; SEQ ID NO: 274, SEQ ID NO: 275, SEQ
ID NO: 276, SEQ ID NO: 634, SEQ ID NO: 635, and SEQ ID NO: 636; SEQ ID NO:
280, SEQ ID NO: 281, SEQ ID NO: 282, SEQ ID NO: 640, SEQ ID NO: 641, and SEQ ID NO:

642; SEQ ID NO: 286, SEQ ID NO: 287, SEQ ID NO: 288, SEQ ID NO: 646, SEQ ID
NO:
647, and SEQ ID NO: 648; SEQ ID NO: 292, SEQ ID NO: 293, SEQ ID NO: 294, SEQ
ID
NO: 652, SEQ ID NO: 653, and SEQ ID NO: 654; SEQ ID NO: 298, SEQ ID NO: 299, SEQ
ID NO: 300, SEQ ID NO: 658, SEQ ID NO: 659, and SEQ ID NO: 660; SEQ ID NO:
304, SEQ ID NO: 305, SEQ ID NO: 306, SEQ ID NO: 664, SEQ ID NO: 665, and SEQ ID NO:

666; SEQ ID NO: 310, SEQ ID NO: 311, SEQ ID NO: 312, SEQ ID NO: 670, SEQ ID
NO:
671, and SEQ ID NO: 672; SEQ ID NO: 316, SEQ ID NO: 317, SEQ ID NO: 318, SEQ
ID
NO: 676, SEQ ID NO: 677, and SEQ ID NO: 678; SEQ ID NO: 322, SEQ ID NO: 323, SEQ
ID NO: 324, SEQ ID NO: 682, SEQ ID NO: 683, and SEQ ID NO: 684; SEQ ID NO:
328, SEQ ID NO: 329, SEQ ID NO: 330, SEQ ID NO: 688, SEQ ID NO: 689, and SEQ ID NO:

690; SEQ ID NO: 334, SEQ ID NO: 335, SEQ ID NO: 336, SEQ ID NO: 694, SEQ ID
NO:
695, and SEQ ID NO: 696; SEQ ID NO: 340, SEQ ID NO: 341, SEQ ID NO: 342, SEQ
ID
NO: 700, SEQ ID NO: 701, and SEQ ID NO: 702; SEQ ID NO: 346, SEQ ID NO: 347, SEQ
ID NO: 348, SEQ ID NO: 706, SEQ ID NO: 707, and SEQ ID NO: 708; SEQ ID NO:
352, SEQ ID NO: 353, SEQ ID NO: 354, SEQ ID NO: 712, SEQ ID NO: 713, and SEQ ID NO:

714; SEQ ID NO: 358, SEQ ID NO: 359, SEQ ID NO: 360, SEQ ID NO: 718, SEQ ID
NO:
719, and SEQ ID NO: 720; SEQ ID NO: 1290, SEQ ID NO: 1291, SEQ ID NO: 1292, SEQ
ID NO: 1293, SEQ ID NO: 1294, and SEQ ID NO: 1295; SEQ ID NO: 1300, SEQ ID NO:

1301, SEQ ID NO: 1302, SEQ ID NO: 1303, SEQ ID NO: 1304, and SEQ ID NO: 1305;
SEQ ID NO: 1310, SEQ ID NO: 1311, SEQ ID NO: 1312, SEQ ID NO: 1313, SEQ ID NO:

1314, and SEQ ID NO: 1315; SEQ ID NO: 1320, SEQ ID NO: 1321, SEQ ID NO: 1322, SEQ ID NO: 1323, SEQ ID NO: 1324, and SEQ ID NO: 1325; SEQ ID NO: 1330, SEQ ID

NO: 1331, SEQ ID NO: 1332, SEQ ID NO: 1333, SEQ ID NO: 1334, and SEQ ID NO:
1335;
SEQ ID NO: 1340, SEQ ID NO: 1341, SEQ ID NO: 1342, SEQ ID NO: 1343, SEQ ID NO:

1344, and SEQ ID NO: 1345; SEQ ID NO: 1350, SEQ ID NO: 1351, SEQ ID NO: 1352, SEQ ID NO: 1353, SEQ ID NO: 1354, and SEQ ID NO: 1355; and SEQ ID NO: 1360, SEQ
ID NO: 1361, SEQ ID NO: 1362, SEQ ID NO: 1363, SEQ ID NO: 1364, and SEQ ID NO:

1365.

31. The isolated antigen binding protein of claim 21, wherein said antigen binding protein is an antibody or a fragment thereof, and wherein said antibody or fragment thereof comprises a light chain variable region comprising a sequence selected from the group consisting of SEQ ID NOs: 723, 727, 731, 735, 739, 743, 747, 751, 755, 759, 763, 767, 771, 775, 779, 783, 787, 791, 795, 799, 803, 807, 811, 815, 819, 823, 827, 831, 835, 839, 843, 847, 851, 855, 859, 863, 867, 871, 875, 879, 883, 887, 891, 895, 899, 903, 907, 911, 915, 919, 923, 927, 931, 935, 939, 943, 947, 951, 955, 959, 1286, 1296, 1306, 1316, 1326, 1336, 1346, and 1356 and a heavy chain variable region comprising a sequence selected from the group consisting of SEQ ID NOs: 724, 728, 732, 736, 740, 744, 748, 752, 756, 760, 764, 768, 772, 776, 780, 784, 788, 792, 796, 800, 804, 808, 812, 816, 820, 824, 828, 832, 836, 840, 844, 848, 852, 856, 860, 864, 868, 872, 876, 880, 884, 888, 892, 896, 900, 904, 908, 912, 916, 920, 924, 928, 932, 936, 940, 944, 948, 952, 956, 960, 1287, 1297, 1307, 1317, 1327, 1337, 1347, and 1357.

32. The isolated antigen binding protein of claim 21, wherein said antigen binding protein is an antibody or a fragment thereof, and wherein said antibody or fragment thereof comprises a combination of a light chain variable region and a heavy chain variable region selected from the group consisting of a light chain variable region comprising SEQ ID NO:
723 and a heavy chain variable region comprising SEQ ID NO: 724; a light chain variable region comprising SEQ ID NO: 727 and a heavy chain variable region comprising SEQ ID
NO: 728; a light chain variable region comprising SEQ ID NO: 731 and a heavy chain variable region comprising SEQ ID NO: 732; a light chain variable region comprising SEQ
ID NO: 735 and a heavy chain variable region comprising SEQ ID NO: 736; a light chain variable region comprising SEQ ID NO: 739 and a heavy chain variable region comprising SEQ ID NO: 740; a light chain variable region comprising SEQ ID NO: 743 and a heavy chain variable region comprising SEQ ID NO: 744; a light chain variable region comprising SEQ ID NO: 747 and a heavy chain variable region comprising SEQ ID NO: 748; a light chain variable region comprising SEQ ID NO: 751 and a heavy chain variable region comprising SEQ ID NO: 752; a light chain variable region comprising SEQ ID NO:
755 and a heavy chain variable region comprising SEQ ID NO: 756; a light chain variable region comprising SEQ ID NO: 759 and a heavy chain variable region comprising SEQ ID
NO: 760;
a light chain variable region comprising SEQ ID NO: 763 and a heavy chain variable region comprising SEQ ID NO: 764; a light chain variable region comprising SEQ ID NO:
767 and a heavy chain variable region comprising SEQ ID NO: 768; a light chain variable region comprising SEQ ID NO: 771 and a heavy chain variable region comprising SEQ ID
NO: 772;
a light chain variable region comprising SEQ ID NO: 775 and a heavy chain variable region comprising SEQ ID NO: 776; a light chain variable region comprising SEQ ID NO:
779 and a heavy chain variable region comprising SEQ ID NO: 780; a light chain variable region comprising SEQ ID NO: 783 and a heavy chain variable region comprising SEQ ID
NO: 784;
a light chain variable region comprising SEQ ID NO: 787 and a heavy chain variable region comprising SEQ ID NO: 788; a light chain variable region comprising SEQ ID NO:
791 and a heavy chain variable region comprising SEQ ID NO: 792; a light chain variable region comprising SEQ ID NO: 795 and a heavy chain variable region comprising SEQ ID
NO: 796;
a light chain variable region comprising SEQ ID NO: 799 and a heavy chain variable region comprising SEQ ID NO: 800; a light chain variable region comprising SEQ ID NO:
803 and a heavy chain variable region comprising SEQ ID NO: 804; a light chain variable region comprising SEQ ID NO: 807 and a heavy chain variable region comprising SEQ ID
NO: 808;
a light chain variable region comprising SEQ ID NO: 811 and a heavy chain variable region comprising SEQ ID NO: 812; a light chain variable region comprising SEQ ID NO:
815 and a heavy chain variable region comprising SEQ ID NO: 816; a light chain variable region comprising SEQ ID NO: 819 and a heavy chain variable region comprising SEQ ID
NO: 820;
a light chain variable region comprising SEQ ID NO: 823 and a heavy chain variable region comprising SEQ ID NO: 824; a light chain variable region comprising SEQ ID NO:
827 and a heavy chain variable region comprising SEQ ID NO: 828; a light chain variable region comprising SEQ ID NO: 831 and a heavy chain variable region comprising SEQ ID
NO: 832;
a light chain variable region comprising SEQ ID NO: 835 and a heavy chain variable region comprising SEQ ID NO: 836; a light chain variable region comprising SEQ ID NO:
839 and a heavy chain variable region comprising SEQ ID NO: 840; a light chain variable region comprising SEQ ID NO: 843 and a heavy chain variable region comprising SEQ ID
NO: 844;
a light chain variable region comprising SEQ ID NO: 847 and a heavy chain variable region comprising SEQ ID NO: 848; a light chain variable region comprising SEQ ID NO:
851 and a heavy chain variable region comprising SEQ ID NO: 852; a light chain variable region comprising SEQ ID NO: 855 and a heavy chain variable region comprising SEQ ID
NO: 856;
a light chain variable region comprising SEQ ID NO: 859 and a heavy chain variable region comprising SEQ ID NO: 860; a light chain variable region comprising SEQ ID NO:
863 and a heavy chain variable region comprising SEQ ID NO: 864; a light chain variable region comprising SEQ ID NO: 867 and a heavy chain variable region comprising SEQ ID
NO: 868;
a light chain variable region comprising SEQ ID NO: 871 and a heavy chain variable region comprising SEQ ID NO: 872; a light chain variable region comprising SEQ ID NO:
875 and a heavy chain variable region comprising SEQ ID NO: 876; a light chain variable region comprising SEQ ID NO: 879 and a heavy chain variable region comprising SEQ ID
NO: 880;
a light chain variable region comprising SEQ ID NO: 883 and a heavy chain variable region comprising SEQ ID NO: 884; a light chain variable region comprising SEQ ID NO:
887 and a heavy chain variable region comprising SEQ ID NO: 888; a light chain variable region comprising SEQ ID NO: 891 and a heavy chain variable region comprising SEQ ID
NO: 892;
a light chain variable region comprising SEQ ID NO: 895 and a heavy chain variable region comprising SEQ ID NO: 896; a light chain variable region comprising SEQ ID NO:
899 and a heavy chain variable region comprising SEQ ID NO: 900; a light chain variable region comprising SEQ ID NO: 903 and a heavy chain variable region comprising SEQ ID
NO: 904;
a light chain variable region comprising SEQ ID NO: 907 and a heavy chain variable region comprising SEQ ID NO: 908; a light chain variable region comprising SEQ ID NO:
911 and a heavy chain variable region comprising SEQ ID NO: 912; a light chain variable region comprising SEQ ID NO: 915 and a heavy chain variable region comprising SEQ ID
NO: 916;
a light chain variable region comprising SEQ ID NO: 919 and a heavy chain variable region comprising SEQ ID NO: 920; a light chain variable region comprising SEQ ID NO:
923 and a heavy chain variable region comprising SEQ ID NO: 924; a light chain variable region comprising SEQ ID NO: 927 and a heavy chain variable region comprising SEQ ID
NO: 928;
a light chain variable region comprising SEQ ID NO: 931 and a heavy chain variable region comprising SEQ ID NO: 932; a light chain variable region comprising SEQ ID NO:
935 and a heavy chain variable region comprising SEQ ID NO: 936; a light chain variable region comprising SEQ ID NO: 939 and a heavy chain variable region comprising SEQ ID
NO: 940;
a light chain variable region comprising SEQ ID NO: 943 and a heavy chain variable region comprising SEQ ID NO: 944; a light chain variable region comprising SEQ ID NO:
947 and a heavy chain variable region comprising SEQ ID NO: 948; a light chain variable region comprising SEQ ID NO: 951 and a heavy chain variable region comprising SEQ ID
NO: 952;
a light chain variable region comprising SEQ ID NO: 955 and a heavy chain variable region comprising SEQ ID NO: 956; a light chain variable region comprising SEQ ID NO:
959 and a heavy chain variable region comprising SEQ ID NO: 960; a light chain variable region comprising SEQ ID NO: 1286 and a heavy chain variable region comprising SEQ ID
NO:
1287; a light chain variable region comprising SEQ ID NO: 1296 and a heavy chain variable region comprising SEQ ID NO: 1297; a light chain variable region comprising SEQ ID NO:
1306 and a heavy chain variable region comprising SEQ ID NO: 1307; a light chain variable region comprising SEQ ID NO: 1316 and a heavy chain variable region comprising SEQ ID
NO: 1317; a light chain variable region comprising SEQ ID NO: 1326 and a heavy chain variable region comprising SEQ ID NO: 1327; a light chain variable region comprising SEQ
ID NO: 1336 and a heavy chain variable region comprising SEQ ID NO: 1337; a light chain variable region comprising SEQ ID NO: 1346 and a heavy chain variable region comprising SEQ ID NO: 1347; and a light chain variable region comprising SEQ ID NO: 1356 and a heavy chain variable region comprising SEQ ID NO: 1357.

33. The isolated antigen binding protein of claim 21, wherein said antigen binding protein is an antibody, and wherein said antibody comprises a light chain comprising a sequence selected from the group consisting of SEQ ID NOs: 963, 967, 971, 975, 979, 983, 987, 991, 995, 999, 1003, 1007, 1011, 1015, 1019, 1023, 1027, 1031, 1035, 1039, 1043, 1047, 1051, 1055, 1059, 1063, 1067, 1071, 1075, 1079, 1083, 1087, 1091, 1095, 1099, 1103, 1107, 111 and a heavy chain comprising a sequence selected from the group consisting of SEQ ID NOs:
964, 968, 972, 976, 980, 984, 988, 992, 996, 1000, 1004, 1008, 1012, 1016, 1020, 1024, 1028, 1032, 1036, 1040, 1044, 1048, 1052, 1056, 1060, 1064, 1068, 1072, 1076, 1080, 1084, 1088, 1092, 1096, 1100, 1104, 1108, 1112, 1116, 1120, 1124, 1128, 1132, 1136, 1140, 1144, 1148, 1152, 1156, 1160, 1164, 1168, 1172, 1176, 1180, 1184, 1188, 1192, 1196, 1200, 1289, 1299, 1309, 1319, 1329, 1339, 1349, and 1359.

34. The isolated antigen binding protein of claim 21, wherein said antigen binding protein is an antibody, and wherein said antibody comprises a combination of a light chain and a heavy chain selected from the group consisting of a light chain comprising SEQ
ID NO: 963 and a heavy chain comprising SEQ ID NO: 964; a light chain comprising SEQ ID
NO: 967 and a heavy chain comprising SEQ ID NO: 968; a light chain comprising SEQ ID
NO: 971 and a heavy chain comprising SEQ ID NO: 972; a light chain comprising SEQ ID
NO: 975 and a heavy chain comprising SEQ ID NO: 976; a light chain comprising SEQ ID
NO: 979 and a heavy chain comprising SEQ ID NO: 980; a light chain comprising SEQ ID
NO: 983 and a heavy chain comprising SEQ ID NO: 984; a light chain comprising SEQ ID
NO: 987 and a heavy chain comprising SEQ ID NO: 988; a light chain comprising SEQ ID
NO: 991 and a heavy chain comprising SEQ ID NO: 992; a light chain comprising SEQ ID
NO: 995 and a heavy chain comprising SEQ ID NO: 996; a light chain comprising SEQ ID
NO: 999 and a heavy chain comprising SEQ ID NO: 1000; a light chain comprising SEQ ID
NO: 1003 and a heavy chain comprising SEQ ID NO: 1004; a light chain comprising SEQ ID
NO: 1007 and a heavy chain comprising SEQ ID NO: 1008; a light chain comprising SEQ ID
NO: 1011 and a heavy chain comprising SEQ ID NO: 1012; a light chain comprising SEQ ID
NO: 1015 and a heavy chain comprising SEQ ID NO: 1016; a light chain comprising SEQ ID
NO: 1019 and a heavy chain comprising SEQ ID NO: 1020; a light chain comprising SEQ ID
NO: 1023 and a heavy chain comprising SEQ ID NO: 1024; a light chain comprising SEQ ID
NO: 1027 and a heavy chain comprising SEQ ID NO: 1028; a light chain comprising SEQ ID
NO: 1031 and a heavy chain comprising SEQ ID NO: 1032; a light chain comprising SEQ ID
NO: 1035 and a heavy chain comprising SEQ ID NO: 1036; a light chain comprising SEQ ID
NO: 1039 and a heavy chain comprising SEQ ID NO: 1040; a light chain comprising SEQ ID
NO: 1043 and a heavy chain comprising SEQ ID NO: 1044; a light chain comprising SEQ ID
NO: 1047 and a heavy chain comprising SEQ ID NO: 1048; a light chain comprising SEQ ID
NO: 1051 and a heavy chain comprising SEQ ID NO: 1052; a light chain comprising SEQ ID
NO: 1055 and a heavy chain comprising SEQ ID NO: 1056; a light chain comprising SEQ ID
NO: 1059 and a heavy chain comprising SEQ ID NO: 1060; a light chain comprising SEQ ID
NO: 1063 and a heavy chain comprising SEQ ID NO: 1064; a light chain comprising SEQ ID
NO: 1067 and a heavy chain comprising SEQ ID NO: 1068; a light chain comprising SEQ ID
NO: 1071 and a heavy chain comprising SEQ ID NO: 1072; a light chain comprising SEQ ID
NO: 1075 and a heavy chain comprising SEQ ID NO: 1076; a light chain comprising SEQ ID
NO: 1079 and a heavy chain comprising SEQ ID NO: 1080; a light chain comprising SEQ ID
NO: 1083 and a heavy chain comprising SEQ ID NO: 1084; a light chain comprising SEQ ID
NO: 1087 and a heavy chain comprising SEQ ID NO: 1088; a light chain comprising SEQ ID
NO: 1091 and a heavy chain comprising SEQ ID NO: 1092; a light chain comprising SEQ ID
NO: 1095 and a heavy chain comprising SEQ ID NO: 1096; a light chain comprising SEQ ID
NO: 1099 and a heavy chain comprising SEQ ID NO: 1100; a light chain comprising SEQ ID
NO: 1103 and a heavy chain comprising SEQ ID NO: 1104; a light chain comprising SEQ ID
NO: 1107 and a heavy chain comprising SEQ ID NO: 1108; a light chain comprising SEQ ID
NO: 1111 and a heavy chain comprising SEQ ID NO: 1112; a light chain comprising SEQ ID
NO: 1115 and a heavy chain comprising SEQ ID NO: 1116; a light chain comprising SEQ ID
NO: 1119 and a heavy chain comprising SEQ ID NO: 1120; a light chain comprising SEQ ID
NO: 1123 and a heavy chain comprising SEQ ID NO: 1124; a light chain comprising SEQ ID
NO: 1127 and a heavy chain comprising SEQ ID NO: 1128; a light chain comprising SEQ ID
NO: 1131 and a heavy chain comprising SEQ ID NO: 1132; a light chain comprising SEQ ID
NO: 1135 and a heavy chain comprising SEQ ID NO: 1136; a light chain comprising SEQ ID
NO: 1139 and a heavy chain comprising SEQ ID NO: 1140; a light chain comprising SEQ ID
NO: 1143 and a heavy chain comprising SEQ ID NO: 1144; a light chain comprising SEQ ID
NO: 1147 and a heavy chain comprising SEQ ID NO: 1148; a light chain comprising SEQ ID
NO: 1151 and a heavy chain comprising SEQ ID NO: 1152; a light chain comprising SEQ ID
NO: 1155 and a heavy chain comprising SEQ ID NO: 1156; a light chain comprising SEQ ID
NO: 1159 and a heavy chain comprising SEQ ID NO: 1160; a light chain comprising SEQ ID
NO: 1163 and a heavy chain comprising SEQ ID NO: 1164; a light chain comprising SEQ ID
NO: 1167 and a heavy chain comprising SEQ ID NO: 1168; a light chain comprising SEQ ID
NO: 1171 and a heavy chain comprising SEQ ID NO: 1172; a light chain comprising SEQ ID
NO: 1175 and a heavy chain comprising SEQ ID NO: 1176; a light chain comprising SEQ ID
NO: 1179 and a heavy chain comprising SEQ ID NO: 1180; a light chain comprising SEQ ID
NO: 1183 and a heavy chain comprising SEQ ID NO: 1184; a light chain comprising SEQ ID
NO: 1187 and a heavy chain comprising SEQ ID NO: 1188; a light chain comprising SEQ ID
NO: 1191 and a heavy chain comprising SEQ ID NO: 1192; a light chain comprising SEQ ID
NO: 1195 and a heavy chain comprising SEQ ID NO: 1196; a light chain comprising SEQ ID
NO: 1199 and a heavy chain comprising SEQ ID NO: 1200; a light chain comprising SEQ ID
NO: 1288 and a heavy chain comprising SEQ ID NO: 1289; a light chain comprising SEQ ID
NO: 1298 and a heavy chain comprising SEQ ID NO: 1299; a light chain comprising SEQ ID
NO: 1308 and a heavy chain comprising SEQ ID NO: 1309; a light chain comprising SEQ ID
NO: 1318 and a heavy chain comprising SEQ ID NO: 1319; a light chain comprising SEQ ID
NO: 1328 and a heavy chain comprising SEQ ID NO: 1329; a light chain comprising SEQ ID
NO: 1338 and a heavy chain comprising SEQ ID NO: 1339; a light chain comprising SEQ ID
NO: 1348 and a heavy chain comprising SEQ ID NO: 1349; and a light chain comprising SEQ
ID NO:
1358 and a heavy chain comprising SEQ ID NO: 1359.

35. A nucleic acid molecule encoding the antibody or fragment thereof according to any one of claims 29-34.

36. The nucleic acid molecule according to claim 35, wherein said nucleic acid molecule is operably linked to a control sequence.

37. A vector comprising a nucleic acid molecule according to claim 36.

38. A host cell comprising the nucleic acid molecule according to claim 37.

39. An antibody or fragment thereof produced by the host cell of claim 38.

40. A method of making the antibody or fragment thereof according to any one of claims 29-34, comprising the step of preparing said antibody or fragment thereof from a host cell that secretes said antibody.

41. A pharmaceutical composition comprising at least one antibody or fragment thereof according to any one of claims 29-34, and pharmaceutically acceptable excipient.

42. An isolated antigen binding protein that competes for binding to the extracellular portion of human GIPR with an antibody or fragment thereof of one of claims 29-34.

43. A composition comprising a therapeutically effective amount of a GLP-1 receptor agonist and a therapeutically effective amount of a GIPR antagonist that specifically binds to a protein having an amino acid sequence having at least 90% amino acid sequence identity to an amino acid sequence of a GIPR.

44. The composition of claim 43, wherein the molar ratio of a GLP-1 receptor agonist to a GIPR antagonist is from about 1:1 to 1:110, 1:1 to 1:100, 1:1 to 1:75, 1:1 to 1:50, 1:1 to 1:25, 1:1 to 1:10, 1:1 to 1:5, and 1:1.

45. The composition of claim 43, wherein the molar ratio of a GIPR
antagonist to a GLP-1 receptor agonist is from about 1:1 to 1:110, 1:1 to 1:100, 1:1 to 1:75, 1:1 to 1:50, 1:1 to 1:25, 1:1 to 1:10, and 1:1 to 1:5.

46. The composition of claim 43, wherein the GLP-1 receptor agonist is used in combination with the GIPR antagonist at therapeutically effective molar ratios of between about 1:1.5 to 1:150, preferably 1:2 to 1:50.

47. The composition of claim 43, wherein the GLP-1 receptor agonist and the GIPR antagonist are present in doses that are at least about 1.1 to 1.4, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, or 10 fold lower than the doses of each compound alone required to treat a condition and/or disease.

48. The composition of claim 43, wherein the GLP-1 receptor agonist is GLP-1(7-37) or a GLP-1(7-37) analog.

49. The composition of claim 48, wherein the GLP-1 receptor agonist is selected from the group consisting of exenatide, liraglutide, lixisenatide, albiglutide, dulaglutide, semaglutide, and taspoglutide.

50. The composition of claim 43, wherein the GLP-1 receptor agonist is selected from the group consisting of GLP-1(7-37) (SEQ ID NO: 1244); GLP-1(7-36)-NH2 (SEQ ID
NO: 1245); liraglutide; albiglutide; taspoglutide; dulaglutide, seinaglutide, LY2428757;
desamino-His7,Arg26,Lys34(Nc-(7-G1u(N-a-hexadecan.oy1)))-(11T-1(7-37) (core peptide disclosed as SEQ ID NO: 1282); desamino-His7,Arg26;Lys34(N c-octanoyl)-GLP-1(7-37) (SEQ

ID NO: 1283); Arg26.34;Lys38(N.epsilon.-(co-carboxypentadecanoyl))-GLP-1(7-38) (SEQ ID NO:
1284); Arg26,34,Lys36(N.epsilon.-(.gamma.-Glu(N-.alpha.-hexadecanoyl)))-GLP-1(7-36) (core peptide disclosed as SEQ ID NO: 1285); Aib8,35,Arg26,34,Phe31-GLP-1(7-36)) (SEQ ID NO: 1246);
HXaa8EGTFTSDVSSYLEXaa22Xaa23AAKEFIXaa30WLXaa33Xaa34G Xaa36Xaa37; wherein Xaa8 is A, V, or G; Xaa22 is G, K, or E; Xaa23 is Q or K; Xaa30 is A or E;
Xaa33 is V or K;
Xaa34 is K, N, or R; Xaa36 is R or G; and Xaa37 is G, H, P, or absent (SEQ ID
NO: 1247);
Arg34-GLP-1(7-37) (SEQ ID NO: 1248); Glu30-GLP-1(7-37) (SEQ ID NO: 1249);
Lys22-GLP-1(7-37) (SEQ ID NO: 1250); Gly8,36,Glu22-GLP-1(7-37) (SEQ ID NO: 1251);
Val8,Glu22,Gly36-GLP-1(7-37) (SEQ ID NO: 1252); Gly8,36,Glu22,Lys33,Asn34-GLP-1(7-37) (SEQ ID NO: 1253); Val8,Glu22,Lys33,Asn34,Gly36-GLP-1(7-37) (SEQ ID NO: 1254);

Gly8,36,Glu22,Pro37-GLP-1(7-37) (SEQ ID NO: 1255); Val8,Glu22,Gly36Pro37-GLP-1(7-37) (SEQ ID NO: 1256); Gly8,36,Glu22,Lys33, Asn34,Pro37-GLP-1(7-37) (SEQ ID NO:
1257);
Val8,Glu22,Lys33,Asn34,GLy36,Pro37-GLP-1(7-37) (SEQ ID NO: 1258);
Gly8,36,Glu22-GLP-1(7-36) (SEQ ID NO: 1259); Val8,Glu22,Gly36-GLP-1(7-36) (SEQ ID NO: 1260);
Val8,Glu22,Asn34,Gly36-GLP-1(7-36) (SEQ ID NO: 1261); and Gly8,36,Glu22,Asn34-GLP-1(7-36) (SEQ ID NO: 1262).

51. The composition of claim 43, wherein human GIPR has a sequence comprising a sequence selected from the group consisting of SEQ ID NO: 1201, SEQ ID NO:
1203, and SEQ ID NO: 1205.

52. The composition of claim 43, wherein the GIPR antagonist is an antigen binding protein.

53. The composition of claim 52, wherein the antigen binding protein is a monoclonal antibody, a polyclonal antibody, a recombinant antibody, a human antibody, a humanized antibody, a chimeric antibody, a multispecific antibody, or an antibody fragment thereof

54. The composition of claim 53, wherein the antibody fragment is a Fab fragment, a Fab' fragment, or a F(ab')2 fragment.

55. The composition of claim 53, wherein the antigen binding protein is a human antibody.

56. The composition of claim 53, wherein the antigen binding protein is a monoclonal antibody.

57. The composition of claim 53, wherein the antigen binding protein is of the IgG1-, IgG2- IgG3- or IgG4-type.

58. The composition of claim 57, wherein the antigen binding protein is of the IgG1- or the IgG2-type.

59. The composition of claim 53, wherein the antigen binding protein is coupled to a labeling group.

60. The composition of claim 53, wherein the antigen binding protein inhibits binding of GIP to the extracellular portion of human GIPR.

61. The composition of claim 53, wherein the antigen binding protein is an antibody or a fragment thereof, and wherein the antibody comprises a CDRL1, a CDRL2, a CDRL3, a CDRH1, a CDRH2, and a CDRH3, wherein the CDRL1 comprises a sequence selected from the group consisting of SEQ ID NOs: 4, 10, 16, 22, 28, 34, 40, 46, 52, 58, 64, 70, 76, 82, 88, 94, 100, 106, 112, 118, 124, 130, 136, 142, 148, 154, 160, 166, 172, 178, 184, 190, 196, 202, 208, 214, 220, 226, 232, 238, 244, 250, 256, 262, 268, 274, 280, 286, 292, 298, 304, 310, 316, 322, 328, 334, 340, 346, 352, 358, 1290, 1300, 1310, 1320, 1330, 1340, and 1350; the CDRL2 comprises a sequence selected from the group consisting of SEQ ID
NOs: 5, 11, 17, 23, 29, 35, 41, 47, 53, 59, 65, 71, 77, 83, 89, 95, 101, 107, 113, 119, 125, 131, 137, 143, 149, 155, 161, 167, 173, 179, 185, 191, 197, 203, 209, 215, 221, 227, 233, 239, 245, 251, 257, 263, 269, 275, 281, 287, 293, 299, 305, 311, 317, 323, 329, 335, 341, 347, 353, 359, 1291, 1301, 1311, 1321, 1331, 1341, and 1351; the CDRL3 comprises a sequence selected from the group consisting of SEQ ID NOs: 6, 12, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, 102, 108, 114, 120, 126, 132, 138, 144, 150, 156, 162, 168, 174, 180, 186, 192, 198, 204, 210, 216, 222, 228, 234, 240, 246, 252, 258, 264, 270, 276, 282, 288, 294, 300, 306, 312, 318, 324, 330, 336, 342, 348, 354, 360, 1292, 1302, 1312, 1322, 1332, 1342, and 1352; the CDRH1 comprises a sequence selected from the group consisting of SEQ ID
NOs: 364, 370, 376, 382, 388, 394, 400, 406, 412, 418, 424, 430, 436, 442, 448, 454, 460, 466, 472, 478, 484, 490, 496, 502, 508, 514, 520, 526, 532, 538, 544, 550, 556, 562, 568, 574, 580, 586, 592, 598, 604, 610, 616, 622, 628, 634, 640, 646, 652, 658, 664, 670, 676, 682, 688, 694, 700, 706, 712, 718, 1293, 1303, 1313, 1323, 1333, 1343, and 1353; the CDRH2 comprises a sequence selected from the group consisting of SEQ ID NOs:
365, 371, 377, 383, 389, 395, 401, 407, 413, 419, 425, 431, 437, 443, 449, 455, 461, 467, 473, 479, 485,491,497,503,509,515,521,527,533,539,545,551,557,563,569,575,581,587, 593, 599, 605, 611, 617, 623, 629, 635, 641, 647, 653, 659, 665, 671, 677, 683, 689, 695, 701, 707, 713, 719, 1294, 1304, 1314, 1324, 1334, 1344, and 1354; and the comprises a sequence selected from the group consisting of SEQ ID NOs: 366, 372, 378, 384, 390, 396, 402, 408, 414, 420, 426, 432, 438, 444, 450, 456, 462, 468, 474, 480, 486, 492, 498, 504, 510, 516, 522, 528, 534, 540, 546, 552, 558, 564, 570, 576, 582, 588, 594, 600, 606, 612, 618, 624, 630, 636, 642, 648, 654, 660, 666, 672, 678, 684, 690, 696, 702, 708, 714, 720, 1295, 1305, 1315, 1325, 1335, 1345, and 1355.

62. The composition of claim 53, wherein the antigen binding protein is an antibody or a fragment thereof, and wherein the antibody comprises a CDRL1, a CDRL2, a CDRL3, a CDRH1, a CDRH2, and a CDRH3, wherein each CDRL1, CDRL2, CDRL3, CDRH1, CDRH2, and CDRH3, respectively, comprises a sequence selected from the group consisting of SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 364, SEQ ID
NO:
365, and SEQ ID NO: 366; SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID
NO:
370, SEQ ID NO: 371, and SEQ ID NO: 372; SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID
NO:
18, SEQ ID NO: 376, SEQ ID NO: 377, and SEQ ID NO: 378; SEQ ID NO: 22, SEQ ID
NO:
23, SEQ ID NO: 24, SEQ ID NO: 382, SEQ ID NO: 383, and SEQ ID NO: 384; SEQ ID
NO:
28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 388, SEQ ID NO: 389, and SEQ ID
NO:
390; SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 394, SEQ ID NO:
395, and SEQ ID NO: 396; SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO:
400, SEQ ID NO: 401, and SEQ ID NO: 402; SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO:
48, SEQ ID NO: 406, SEQ ID NO: 407, and SEQ ID NO: 408; SEQ ID NO: 52, SEQ ID NO:
53, SEQ ID NO: 54, SEQ ID NO: 412, SEQ ID NO: 413, and SEQ ID NO: 414; SEQ ID NO:
58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 418, SEQ ID NO: 419, and SEQ ID NO:
420;
SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 424, SEQ ID NO: 425, and SEQ ID NO: 426; SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 430, SEQ
ID NO: 431, and SEQ ID NO: 432; SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ
ID NO: 436, SEQ ID NO: 437, and SEQ ID NO: 438; SEQ ID NO: 82, SEQ ID NO: 83, SEQ
ID NO: 84, SEQ ID NO: 442, SEQ ID NO: 443, and SEQ ID NO: 444; SEQ ID NO: 88, SEQ
ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 448, SEQ ID NO: 449, and SEQ ID NO: 450;
SEQ
ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 454, SEQ ID NO: 455, and SEQ
ID NO: 456; SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 460, SEQ
ID NO: 461, and SEQ ID NO: 462; SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO:
108, SEQ ID NO: 466, SEQ ID NO: 467, and SEQ ID NO: 468; SEQ ID NO: 112, SEQ ID NO:

113, SEQ ID NO: 114, SEQ ID NO: 472, SEQ ID NO: 473, and SEQ ID NO: 474; SEQ
ID

NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO: 478, SEQ ID NO: 479, and SEQ
ID NO: 480; SEQ ID NO: 124, SEQ ID NO: 125, SEQ ID NO: 126, SEQ ID NO: 484, SEQ
ID NO: 485, and SEQ ID NO: 486; SEQ ID NO: 130, SEQ ID NO: 131, SEQ ID NO:
132, SEQ ID NO: 490, SEQ ID NO: 491, and SEQ ID NO: 492; SEQ ID NO: 136, SEQ ID NO:

137, SEQ ID NO: 138, SEQ ID NO: 496, SEQ ID NO: 497, and SEQ ID NO: 498; SEQ
ID
NO: 142, SEQ ID NO: 143, SEQ ID NO: 144, SEQ ID NO: 502, SEQ ID NO: 503, and SEQ
ID NO: 504; SEQ ID NO: 148, SEQ ID NO: 149, SEQ ID NO: 150, SEQ ID NO: 508, SEQ
ID NO: 509, and SEQ ID NO: 510; SEQ ID NO: 154, SEQ ID NO: 155, SEQ ID NO:
156, SEQ ID NO: 514, SEQ ID NO: 515, and SEQ ID NO: 516; SEQ ID NO: 160, SEQ ID NO:

161, SEQ ID NO: 162, SEQ ID NO: 520, SEQ ID NO: 521, and SEQ ID NO: 522; SEQ
ID
NO: 166, SEQ ID NO: 167, SEQ ID NO: 168, SEQ ID NO: 526, SEQ ID NO: 527, and SEQ
ID NO: 528; SEQ ID NO: 172, SEQ ID NO: 173, SEQ ID NO: 174, SEQ ID NO: 532, SEQ
ID NO: 533, and SEQ ID NO: 534; SEQ ID NO: 178, SEQ ID NO: 179, SEQ ID NO:
180, SEQ ID NO: 538, SEQ ID NO: 539, and SEQ ID NO: 540; SEQ ID NO: 184, SEQ ID NO:

185, SEQ ID NO: 186, SEQ ID NO: 544, SEQ ID NO: 545, and SEQ ID NO: 546; SEQ
ID
NO: 190, SEQ ID NO: 191, SEQ ID NO: 192, SEQ ID NO: 550, SEQ ID NO: 551, and SEQ
ID NO: 552; SEQ ID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 556, SEQ
ID NO: 557, and SEQ ID NO: 558; SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO:
204, SEQ ID NO: 562, SEQ ID NO: 563, and SEQ ID NO: 564; SEQ ID NO: 208, SEQ ID NO:

209, SEQ ID NO: 210, SEQ ID NO: 568, SEQ ID NO: 569, and SEQ ID NO: 570; SEQ
ID
NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 574, SEQ ID NO: 575, and SEQ
ID NO: 576; SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 580, SEQ
ID NO: 581, and SEQ ID NO: 582; SEQ ID NO: 226, SEQ ID NO: 227, SEQ ID NO:
228, SEQ ID NO: 586, SEQ ID NO: 587, and SEQ ID NO: 588; SEQ ID NO: 232, SEQ ID NO:

233, SEQ ID NO: 234, SEQ ID NO: 592, SEQ ID NO: 593, and SEQ ID NO: 594; SEQ
ID
NO: 238, SEQ ID NO: 239, SEQ ID NO: 240, SEQ ID NO: 598, SEQ ID NO: 599, and SEQ
ID NO: 600; SEQ ID NO: 244, SEQ ID NO: 245, SEQ ID NO: 246, SEQ ID NO: 604, SEQ
ID NO: 605, and SEQ ID NO: 606; SEQ ID NO: 250, SEQ ID NO: 251, SEQ ID NO:
252, SEQ ID NO: 610, SEQ ID NO: 611, and SEQ ID NO: 612; SEQ ID NO: 256, SEQ ID NO:

257, SEQ ID NO: 258, SEQ ID NO: 616, SEQ ID NO: 617, and SEQ ID NO: 618; SEQ
ID
NO: 262, SEQ ID NO: 263, SEQ ID NO: 264, SEQ ID NO: 622, SEQ ID NO: 623, and SEQ
ID NO: 624; SEQ ID NO: 268, SEQ ID NO: 269, SEQ ID NO: 270, SEQ ID NO: 628, SEQ
ID NO: 629, and SEQ ID NO: 630; SEQ ID NO: 274, SEQ ID NO: 275, SEQ ID NO:
276, SEQ ID NO: 634, SEQ ID NO: 635, and SEQ ID NO: 636; SEQ ID NO: 280, SEQ ID NO:

281, SEQ ID NO: 282, SEQ ID NO: 640, SEQ ID NO: 641, and SEQ ID NO: 642; SEQ
ID
NO: 286, SEQ ID NO: 287, SEQ ID NO: 288, SEQ ID NO: 646, SEQ ID NO: 647, and SEQ
ID NO: 648; SEQ ID NO: 292, SEQ ID NO: 293, SEQ ID NO: 294, SEQ ID NO: 652, SEQ
ID NO: 653, and SEQ ID NO: 654; SEQ ID NO: 298, SEQ ID NO: 299, SEQ ID NO:
300, SEQ ID NO: 658, SEQ ID NO: 659, and SEQ ID NO: 660; SEQ ID NO: 304, SEQ ID NO:

305, SEQ ID NO: 306, SEQ ID NO: 664, SEQ ID NO: 665, and SEQ ID NO: 666; SEQ
ID
NO: 310, SEQ ID NO: 311, SEQ ID NO: 312, SEQ ID NO: 670, SEQ ID NO: 671, and SEQ
ID NO: 672; SEQ ID NO: 316, SEQ ID NO: 317, SEQ ID NO: 318, SEQ ID NO: 676, SEQ
ID NO: 677, and SEQ ID NO: 678; SEQ ID NO: 322, SEQ ID NO: 323, SEQ ID NO:
324, SEQ ID NO: 682, SEQ ID NO: 683, and SEQ ID NO: 684; SEQ ID NO: 328, SEQ ID NO:

329, SEQ ID NO: 330, SEQ ID NO: 688, SEQ ID NO: 689, and SEQ ID NO: 690; SEQ
ID
NO: 334, SEQ ID NO: 335, SEQ ID NO: 336, SEQ ID NO: 694, SEQ ID NO: 695, and SEQ
ID NO: 696; SEQ ID NO: 340, SEQ ID NO: 341, SEQ ID NO: 342, SEQ ID NO: 700, SEQ
ID NO: 701, and SEQ ID NO: 702; SEQ ID NO: 346, SEQ ID NO: 347, SEQ ID NO:
348, SEQ ID NO: 706, SEQ ID NO: 707, and SEQ ID NO: 708; SEQ ID NO: 352, SEQ ID NO:

353, SEQ ID NO: 354, SEQ ID NO: 712, SEQ ID NO: 713, and SEQ ID NO: 714; SEQ
ID
NO: 358, SEQ ID NO: 359, SEQ ID NO: 360, SEQ ID NO: 718, SEQ ID NO: 719, and SEQ
ID NO: 720; SEQ ID NO: 1290, SEQ ID NO: 1291, SEQ ID NO: 1292, SEQ ID NO:
1293, SEQ ID NO: 1294, and SEQ ID NO: 1295; SEQ ID NO: 1300, SEQ ID NO: 1301, SEQ ID

NO: 1302, SEQ ID NO: 1303, SEQ ID NO: 1304, and SEQ ID NO: 1305; SEQ ID NO:
1310, SEQ ID NO: 1311, SEQ ID NO: 1312, SEQ ID NO: 1313, SEQ ID NO: 1314, and SEQ ID

NO: 1315; SEQ ID NO: 1320, SEQ ID NO: 1321, SEQ ID NO: 1322, SEQ ID NO: 1323, SEQ ID NO: 1324, and SEQ ID NO: 1325; SEQ ID NO: 1330, SEQ ID NO: 1331, SEQ ID

NO: 1332, SEQ ID NO: 1333, SEQ ID NO: 1334, and SEQ ID NO: 1335; SEQ ID NO:
1340, SEQ ID NO: 1341, SEQ ID NO: 1342, SEQ ID NO: 1343, SEQ ID NO: 1344, and SEQ ID

NO: 1345; SEQ ID NO: 1350, SEQ ID NO: 1351, SEQ ID NO: 1352, SEQ ID NO: 1353, SEQ ID NO: 1354, and SEQ ID NO: 1355; and SEQ ID NO: 1360, SEQ ID NO: 1361, SEQ
ID NO: 1362, SEQ ID NO: 1363, SEQ ID NO: 1364, and SEQ ID NO: 1365.

63. The composition of claim 53, wherein the antigen binding protein is an antibody or a fragment thereof, and wherein the antibody or fragment thereof comprises a light chain variable region comprising a sequence selected from the group consisting of SEQ
ID NOs:723,727,731,735,739,743,747,751,755,759,763,767,771,775,779,783,787, 791,795,799,803,807,811,815,819,823,827,831,835,839,843,847,851,855,859, 863,867,871,875,879,883,887,891,895,899,903,907,911,915,919,923,927,931, 935, 939, 943, 947, 951, 955, 959, 1286, 1296, 1306, 1316, 1326, 1336, 1346, and 1356 and a heavy chain variable region comprising a sequence selected from the group consisting of SEQ ID NOs: 724, 728, 732, 736, 740, 744, 748, 752, 756, 760, 764, 768, 772, 776, 780, 784, 788, 792, 796, 800, 804, 808, 812, 816, 820, 824, 828, 832, 836, 840, 844, 848, 852, 856, 860, 864, 868, 872, 876, 880, 884, 888, 892, 896, 900, 904, 908, 912, 916, 920, 924, 928, 932, 936, 940, 944, 948, 952, 956, 960, 1287, 1297, 1307, 1317, 1327, 1337, 1347, and 1357.

64. The composition of claim 53, wherein the antigen binding protein is an antibody or a fragment thereof, and wherein the antibody or fragment thereof comprises a combination of a light chain variable region and a heavy chain variable region selected from the group consisting of a light chain variable region comprising SEQ ID NO:
723 and a heavy chain variable region comprising SEQ ID NO: 724; a light chain variable region comprising SEQ ID NO: 727 and a heavy chain variable region comprising SEQ ID NO: 728; a light chain variable region comprising SEQ ID NO: 731 and a heavy chain variable region comprising SEQ ID NO: 732; a light chain variable region comprising SEQ ID NO:
735 and a heavy chain variable region comprising SEQ ID NO: 736; a light chain variable region comprising SEQ ID NO: 739 and a heavy chain variable region comprising SEQ ID
NO: 740;
a light chain variable region comprising SEQ ID NO: 743 and a heavy chain variable region comprising SEQ ID NO: 744; a light chain variable region comprising SEQ ID NO:
747 and a heavy chain variable region comprising SEQ ID NO: 748; a light chain variable region comprising SEQ ID NO: 751 and a heavy chain variable region comprising SEQ ID
NO: 752;
a light chain variable region comprising SEQ ID NO: 755 and a heavy chain variable region comprising SEQ ID NO: 756; a light chain variable region comprising SEQ ID NO:
759 and a heavy chain variable region comprising SEQ ID NO: 760; a light chain variable region comprising SEQ ID NO: 763 and a heavy chain variable region comprising SEQ ID
NO: 764;
a light chain variable region comprising SEQ ID NO: 767 and a heavy chain variable region comprising SEQ ID NO: 768; a light chain variable region comprising SEQ ID NO:
771 and a heavy chain variable region comprising SEQ ID NO: 772; a light chain variable region comprising SEQ ID NO: 775 and a heavy chain variable region comprising SEQ ID
NO: 776;
a light chain variable region comprising SEQ ID NO: 779 and a heavy chain variable region comprising SEQ ID NO: 780; a light chain variable region comprising SEQ ID NO:
783 and a heavy chain variable region comprising SEQ ID NO: 784; a light chain variable region comprising SEQ ID NO: 787 and a heavy chain variable region comprising SEQ ID
NO: 788;
a light chain variable region comprising SEQ ID NO: 791 and a heavy chain variable region comprising SEQ ID NO: 792; a light chain variable region comprising SEQ ID NO:
795 and a heavy chain variable region comprising SEQ ID NO: 796; a light chain variable region comprising SEQ ID NO: 799 and a heavy chain variable region comprising SEQ ID
NO: 800;
a light chain variable region comprising SEQ ID NO: 803 and a heavy chain variable region comprising SEQ ID NO: 804; a light chain variable region comprising SEQ ID NO:
807 and a heavy chain variable region comprising SEQ ID NO: 808; a light chain variable region comprising SEQ ID NO: 811 and a heavy chain variable region comprising SEQ ID
NO: 812;
a light chain variable region comprising SEQ ID NO: 815 and a heavy chain variable region comprising SEQ ID NO: 816; a light chain variable region comprising SEQ ID NO:
819 and a heavy chain variable region comprising SEQ ID NO: 820; a light chain variable region comprising SEQ ID NO: 823 and a heavy chain variable region comprising SEQ ID
NO: 824;
a light chain variable region comprising SEQ ID NO: 827 and a heavy chain variable region comprising SEQ ID NO: 828; a light chain variable region comprising SEQ ID NO:
831 and a heavy chain variable region comprising SEQ ID NO: 832; a light chain variable region comprising SEQ ID NO: 835 and a heavy chain variable region comprising SEQ ID
NO: 836;
a light chain variable region comprising SEQ ID NO: 839 and a heavy chain variable region comprising SEQ ID NO: 840; a light chain variable region comprising SEQ ID NO:
843 and a heavy chain variable region comprising SEQ ID NO: 844; a light chain variable region comprising SEQ ID NO: 847 and a heavy chain variable region comprising SEQ ID
NO: 848;
a light chain variable region comprising SEQ ID NO: 851 and a heavy chain variable region comprising SEQ ID NO: 852; a light chain variable region comprising SEQ ID NO:
855 and a heavy chain variable region comprising SEQ ID NO: 856; a light chain variable region comprising SEQ ID NO: 859 and a heavy chain variable region comprising SEQ ID
NO: 860;
a light chain variable region comprising SEQ ID NO: 863 and a heavy chain variable region comprising SEQ ID NO: 864; a light chain variable region comprising SEQ ID NO:
867 and a heavy chain variable region comprising SEQ ID NO: 868; a light chain variable region comprising SEQ ID NO: 871 and a heavy chain variable region comprising SEQ ID
NO: 872;
a light chain variable region comprising SEQ ID NO: 875 and a heavy chain variable region comprising SEQ ID NO: 876; a light chain variable region comprising SEQ ID NO:
879 and a heavy chain variable region comprising SEQ ID NO: 880; a light chain variable region comprising SEQ ID NO: 883 and a heavy chain variable region comprising SEQ ID
NO: 884;
a light chain variable region comprising SEQ ID NO: 887 and a heavy chain variable region comprising SEQ ID NO: 888; a light chain variable region comprising SEQ ID NO:
891 and a heavy chain variable region comprising SEQ ID NO: 892; a light chain variable region comprising SEQ ID NO: 895 and a heavy chain variable region comprising SEQ ID
NO: 896;

a light chain variable region comprising SEQ ID NO: 899 and a heavy chain variable region comprising SEQ ID NO: 900; a light chain variable region comprising SEQ ID NO:
903 and a heavy chain variable region comprising SEQ ID NO: 904; a light chain variable region comprising SEQ ID NO: 907 and a heavy chain variable region comprising SEQ ID
NO: 908;
a light chain variable region comprising SEQ ID NO: 911 and a heavy chain variable region comprising SEQ ID NO: 912; a light chain variable region comprising SEQ ID NO:
915 and a heavy chain variable region comprising SEQ ID NO: 916; a light chain variable region comprising SEQ ID NO: 919 and a heavy chain variable region comprising SEQ ID
NO: 920;
a light chain variable region comprising SEQ ID NO: 923 and a heavy chain variable region comprising SEQ ID NO: 924; a light chain variable region comprising SEQ ID NO:
927 and a heavy chain variable region comprising SEQ ID NO: 928; a light chain variable region comprising SEQ ID NO: 931 and a heavy chain variable region comprising SEQ ID
NO: 932;
a light chain variable region comprising SEQ ID NO: 935 and a heavy chain variable region comprising SEQ ID NO: 936; a light chain variable region comprising SEQ ID NO:
939 and a heavy chain variable region comprising SEQ ID NO: 940; a light chain variable region comprising SEQ ID NO: 943 and a heavy chain variable region comprising SEQ ID
NO: 944;
a light chain variable region comprising SEQ ID NO: 947 and a heavy chain variable region comprising SEQ ID NO: 948; a light chain variable region comprising SEQ ID NO:
951 and a heavy chain variable region comprising SEQ ID NO: 952; a light chain variable region comprising SEQ ID NO: 955 and a heavy chain variable region comprising SEQ ID
NO: 956;
a light chain variable region comprising SEQ ID NO: 959 and a heavy chain variable region comprising SEQ ID NO: 960; a light chain variable region comprising SEQ ID NO:
1286 and a heavy chain variable region comprising SEQ ID NO: 1287; a light chain variable region comprising SEQ ID NO: 1296 and a heavy chain variable region comprising SEQ ID
NO:
1297; a light chain variable region comprising SEQ ID NO: 1306 and a heavy chain variable region comprising SEQ ID NO: 1307; a light chain variable region comprising SEQ ID NO:
1316 and a heavy chain variable region comprising SEQ ID NO: 1317; a light chain variable region comprising SEQ ID NO: 1326 and a heavy chain variable region comprising SEQ ID
NO: 1327; a light chain variable region comprising SEQ ID NO: 1336 and a heavy chain variable region comprising SEQ ID NO: 1337; a light chain variable region comprising SEQ
ID NO: 1346 and a heavy chain variable region comprising SEQ ID NO: 1347; and a light chain variable region comprising SEQ ID NO: 1356 and a heavy chain variable region comprising SEQ ID NO: 1357.

65. The composition of claim 53, wherein the antigen binding protein is an antibody, and wherein the antibody comprises a light chain comprising a sequence selected from the group consisting of SEQ ID NOs: 963, 967, 971, 975, 979, 983, 987, 991, 995, 999, 1003, 1007, 1011, 1015, 1019, 1023, 1027, 1031, 1035, 1039, 1043, 1047, 1051, 1055, 1059, 1063, 1067, 1071, 1075, 1079, 1083, 1087, 1091, 1095, 1099, 1103, 1107, 111 and a heavy chain comprising a sequence selected from the group consisting of SEQ ID NOs:
964, 968, 972, 976, 980, 984, 988, 992, 996, 1000, 1004, 1008, 1012, 1016, 1020, 1024, 1028, 1032, 1036, 1040, 1044, 1048, 1052, 1056, 1060, 1064, 1068, 1072, 1076, 1080, 1084, 1088, 1092, 1096, 1100, 1104, 1108, 1112, 1116, 1120, 1124, 1128, 1132, 1136, 1140, 1144, 1148, 1152, 1156, 1160, 1164, 1168, 1172, 1176, 1180, 1184, 1188, 1192, 1196, 1200, 1289, 1299, 1309, 1319, 1329, 1339, 1349, and 1359.

66. The composition of claim 53, wherein the antigen binding protein is an antibody, and wherein the antibody comprises a combination of a light chain and a heavy chain selected from the group consisting of a light chain comprising SEQ ID
NO: 963 and a heavy chain comprising SEQ ID NO: 964; a light chain comprising SEQ ID NO: 967 and a heavy chain comprising SEQ ID NO: 968; a light chain comprising SEQ ID NO: 971 and a heavy chain comprising SEQ ID NO: 972; a light chain comprising SEQ ID NO: 975 and a heavy chain comprising SEQ ID NO: 976; a light chain comprising SEQ ID NO: 979 and a heavy chain comprising SEQ ID NO: 980; a light chain comprising SEQ ID NO: 983 and a heavy chain comprising SEQ ID NO: 984; a light chain comprising SEQ ID NO: 987 and a heavy chain comprising SEQ ID NO: 988; a light chain comprising SEQ ID NO: 991 and a heavy chain comprising SEQ ID NO: 992; a light chain comprising SEQ ID NO: 995 and a heavy chain comprising SEQ ID NO: 996; a light chain comprising SEQ ID NO: 999 and a heavy chain comprising SEQ ID NO: 1000; a light chain comprising SEQ ID NO:
1003 and a heavy chain comprising SEQ ID NO: 1004; a light chain comprising SEQ ID NO:
1007 and a heavy chain comprising SEQ ID NO: 1008; a light chain comprising SEQ ID NO:
1011 and a heavy chain comprising SEQ ID NO: 1012; a light chain comprising SEQ ID NO:
1015 and a heavy chain comprising SEQ ID NO: 1016; a light chain comprising SEQ ID NO:
1019 and a heavy chain comprising SEQ ID NO: 1020; a light chain comprising SEQ ID NO:
1023 and a heavy chain comprising SEQ ID NO: 1024; a light chain comprising SEQ ID NO:
1027 and a heavy chain comprising SEQ ID NO: 1028; a light chain comprising SEQ ID NO:
1031 and a heavy chain comprising SEQ ID NO: 1032; a light chain comprising SEQ ID NO:
1035 and a heavy chain comprising SEQ ID NO: 1036; a light chain comprising SEQ ID NO:
1039 and a heavy chain comprising SEQ ID NO: 1040; a light chain comprising SEQ ID NO:
1043 and a heavy chain comprising SEQ ID NO: 1044; a light chain comprising SEQ ID NO:
1047 and a heavy chain comprising SEQ ID NO: 1048; a light chain comprising SEQ ID NO:
1051 and a heavy chain comprising SEQ ID NO: 1052; a light chain comprising SEQ ID NO:
1055 and a heavy chain comprising SEQ ID NO: 1056; a light chain comprising SEQ ID NO:
1059 and a heavy chain comprising SEQ ID NO: 1060; a light chain comprising SEQ ID NO:
1063 and a heavy chain comprising SEQ ID NO: 1064; a light chain comprising SEQ ID NO:
1067 and a heavy chain comprising SEQ ID NO: 1068; a light chain comprising SEQ ID NO:
1071 and a heavy chain comprising SEQ ID NO: 1072; a light chain comprising SEQ ID NO:
1075 and a heavy chain comprising SEQ ID NO: 1076; a light chain comprising SEQ ID NO:
1079 and a heavy chain comprising SEQ ID NO: 1080; a light chain comprising SEQ ID NO:
1083 and a heavy chain comprising SEQ ID NO: 1084; a light chain comprising SEQ ID NO:
1087 and a heavy chain comprising SEQ ID NO: 1088; a light chain comprising SEQ ID NO:
1091 and a heavy chain comprising SEQ ID NO: 1092; a light chain comprising SEQ ID NO:
1095 and a heavy chain comprising SEQ ID NO: 1096; a light chain comprising SEQ ID NO:
1099 and a heavy chain comprising SEQ ID NO: 1100; a light chain comprising SEQ ID NO:
1103 and a heavy chain comprising SEQ ID NO: 1104; a light chain comprising SEQ ID NO:
1107 and a heavy chain comprising SEQ ID NO: 1108; a light chain comprising SEQ ID NO:
1111 and a heavy chain comprising SEQ ID NO: 1112; a light chain comprising SEQ ID NO:
1115 and a heavy chain comprising SEQ ID NO: 1116; a light chain comprising SEQ ID NO:
1119 and a heavy chain comprising SEQ ID NO: 1120; a light chain comprising SEQ ID NO:
1123 and a heavy chain comprising SEQ ID NO: 1124; a light chain comprising SEQ ID NO:
1127 and a heavy chain comprising SEQ ID NO: 1128; a light chain comprising SEQ ID NO:
1131 and a heavy chain comprising SEQ ID NO: 1132; a light chain comprising SEQ ID NO:
1135 and a heavy chain comprising SEQ ID NO: 1136; a light chain comprising SEQ ID NO:
1139 and a heavy chain comprising SEQ ID NO: 1140; a light chain comprising SEQ ID NO:
1143 and a heavy chain comprising SEQ ID NO: 1144; a light chain comprising SEQ ID NO:
1147 and a heavy chain comprising SEQ ID NO: 1148; a light chain comprising SEQ ID NO:
1151 and a heavy chain comprising SEQ ID NO: 1152; a light chain comprising SEQ ID NO:
1155 and a heavy chain comprising SEQ ID NO: 1156; a light chain comprising SEQ ID NO:
1159 and a heavy chain comprising SEQ ID NO: 1160; a light chain comprising SEQ ID NO:
1163 and a heavy chain comprising SEQ ID NO: 1164; a light chain comprising SEQ ID NO:
1167 and a heavy chain comprising SEQ ID NO: 1168; a light chain comprising SEQ ID NO:
1171 and a heavy chain comprising SEQ ID NO: 1172; a light chain comprising SEQ ID NO:
1175 and a heavy chain comprising SEQ ID NO: 1176; a light chain comprising SEQ ID NO:
1179 and a heavy chain comprising SEQ ID NO: 1180; a light chain comprising SEQ ID NO:
1183 and a heavy chain comprising SEQ ID NO: 1184; a light chain comprising SEQ ID NO:
1187 and a heavy chain comprising SEQ ID NO: 1188; a light chain comprising SEQ ID NO:
1191 and a heavy chain comprising SEQ ID NO: 1192; a light chain comprising SEQ ID NO:
1195 and a heavy chain comprising SEQ ID NO: 1196; a light chain comprising SEQ ID NO:
1199 and a heavy chain comprising SEQ ID NO: 1200; a light chain comprising SEQ ID NO:
1288 and a heavy chain comprising SEQ ID NO: 1289; a light chain comprising SEQ ID NO:
1298 and a heavy chain comprising SEQ ID NO: 1299; a light chain comprising SEQ ID NO:
1308 and a heavy chain comprising SEQ ID NO: 1309; a light chain comprising SEQ ID NO:
1318 and a heavy chain comprising SEQ ID NO: 1319; a light chain comprising SEQ ID NO:
1328 and a heavy chain comprising SEQ ID NO: 1329; a light chain comprising SEQ ID NO:
1338 and a heavy chain comprising SEQ ID NO: 1339; a light chain comprising SEQ ID NO:
1348 and a heavy chain comprising SEQ ID NO: 1349; and a light chain comprising SEQ ID
NO: 1358 and a heavy chain comprising SEQ ID NO: 1359.